Displaying publications 41 - 60 of 635 in total

Abstract:
Sort:
  1. Reconstruction of the Austronesian Diaspora in the Era of Genomics
    Chambers GK, Edinur HA
    Hum Biol, 2021 10;92(4):247-263.
    PMID: 34665569 DOI: 10.13110/humanbiology.92.4.04
    The Austronesian Diaspora is a 5,000-year account of how a small group of Taiwanese farmers expanded to occupy territories reaching halfway around the world. Reconstructing their detailed history has spawned many academic contests across many disciplines. An outline orthodox version has eventually emerged but still leaves many unanswered questions. The remarkable power of whole-genome technology has now been applied to people across the entire region. This review gives an account of this era of genetic investigation and discusses its many achievements, including revelation in detail of many unexpected patterns of population movement and the significance of this information for medical genetics.
    Matched MeSH terms: Polymorphism, Single Nucleotide
  2. Case-Control Study and Meta-Analysis of the Association Between LIPG rs9958947 SNP and Stroke Risk
    Phneh KY, Chong ETJ, Shah SS, Chia YK, Daud DMBA, Jalil E, et al.
    J Mol Neurosci, 2021 Oct;71(10):2085-2094.
    PMID: 33479916 DOI: 10.1007/s12031-021-01795-w
    The rs9958947 single nucleotide polymorphism (SNP) resides in the promoter region of the lipase G (LIPG) gene. This newly discovered SNP increases the risk of stroke in some Asian populations, including Chinese and Korean populations. Stroke is one of the top 5 leading causes of death in Malaysia, so it is of interest to investigate whether this SNP is associated with stroke risk in the Malaysian population. Therefore, this study investigates this association through a case-control study on a Malaysian population along with a comprehensive meta-analysis. Genotyping of LIPG rs9958947 SNP was performed for 241 Malaysians using real-time polymerase chain reaction, and the odds ratios (OR) with 95% confidence intervals were calculated. The meta-analysis was conducted using the software Comprehensive Meta-Analysis ver. 2.2.064. A p value less than 0.05 was considered statistically significant. We observed that the mean age of Malaysian stroke patients was less than that of stroke patients from Korea and China. The meta-analysis showed that the LIPG rs9958947 SNP was significantly associated with an increased risk of ischemic stroke in Asian populations (dominant (CC vs. CT + TT): OR = 1.45, p  0.05) and blood lipid levels.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  3. Fulltext The rs9340799 polymorphism of the estrogen receptor alpha (ESR1) gene and its association with breast cancer susceptibility
    Tan SC, Low TY, Mohamad Hanif EA, Sharzehan MAK, Kord-Varkaneh H, Islam MA
    Sci Rep, 2021 Sep 20;11(1):18619.
    PMID: 34545128 DOI: 10.1038/s41598-021-97935-8
    The ESR1 rs9340799 polymorphism has been frequently investigated with regard to its association with breast cancer (BC) susceptibility, but the findings have been inconclusive. In this work, we aimed to address the inconsistencies in study findings by performing a systematic review and meta-analysis. Eligible studies were identified from the Web of Science, PubMed, Scopus, China National Knowledge Infrastructure, VIP and Wanfang databases based on the predefined inclusion and exclusion criteria. The pooled odds ratio (OR) was then calculated under five genetic models: homozygous (GG vs. AA), heterozygous (AG vs. AA), dominant (AG + GG vs. AA), recessive (GG vs. AA + AG) and allele (G vs. A). Combined results from 23 studies involving 34,721 subjects indicated a lack of significant association between the polymorphism and BC susceptibility (homozygous model, OR = 1.045, 95% CI 0.887-1.231, P = 0.601; heterozygous model, OR = 0.941, 95% CI 0.861-1.030, P = 0.186; dominant model, OR = 0.957, 95% CI 0.875-1.045, P = 0.327; recessive model, OR = 1.053, 95% CI 0.908-1.222, P = 0.495; allele model, OR = 0.987, 95% CI 0.919-1.059, P = 0.709). Subgroup analyses by ethnicity, menopausal status and study quality also revealed no statistically significant association (P > 0.05). In conclusion, our results showed that the ESR1 rs9340799 polymorphism was not associated with BC susceptibility, suggesting its limited potential as a genetic marker for BC.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  4. The details are in the genome-wide SNPs: Fine scale evolution of the Malaysian weedy rice
    Sudo MPS, Yesudasan R, Neik TX, Masilamany D, Jayaraj J, Teo SS, et al.
    Plant Sci, 2021 Sep;310:110985.
    PMID: 34315600 DOI: 10.1016/j.plantsci.2021.110985
    Weedy rice (Oryza spp.) is a major nuisance to rice farmers from all over the world. Although the emergence of weedy rice in East Malaysia on the island of Borneo is very recent, the threat to rice yield has reached an alarming stage. Using 47,027 genotyping-by-sequencing (GBS)-derived SNPs and candidate gene analysis of the plant architecture domestication gene TAC1, we assessed the genetic variations and evolutionary origin of weedy rice in East Malaysia. Our findings revealed two major evolutionary paths for genetically distinct weedy rice types. Whilst the cultivar-like weedy rice are very likely to be the weedy descendant of local coexisting cultivars, the wild-like weedy rice appeared to have arisen through two possible routes: (i) accidental introduction from Peninsular Malaysia weedy rice populations, and (ii) weedy descendants of coexisting cultivars. The outcome of our genetic analyses supports the notion that Sabah cultivars and Peninsular Malaysia weedy rice are the potential progenitors of Sabah weedy rice. Similar TAC1 haplotypes were shared between Malaysian cultivated and weedy rice populations, which further supported the findings of our GBS-SNP analyses. These different strains of weedy rice have convergently evolved shared traits, such as seeds shattering and open tillers. A comparison with our previous simple-sequence repeat-based population genetic analyses highlights the strength of genome-wide SNPs, including detection of admixtures and low-level introgression events. These findings could inform better strategic management for controlling the spread of weedy rice in the region.
    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics*
  5. Fulltext Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays
    Khoruddin NA, Noorizhab MN, Teh LK, Mohd Yusof FZ, Salleh MZ
    Sci Rep, 2021 Aug 09;11(1):16158.
    PMID: 34373545 DOI: 10.1038/s41598-021-95618-y
    Single-nucleotide polymorphisms (SNPs) are the most common genetic variations for various complex human diseases, including cancers. Genome-wide association studies (GWAS) have identified numerous SNPs that increase cancer risks, such as breast cancer, colorectal cancer, and leukemia. These SNPs were cataloged for scientific use. However, GWAS are often conducted on certain populations in which the Orang Asli and Malays were not included. Therefore, we have developed a bioinformatic pipeline to mine the whole-genome sequence databases of the Orang Asli and Malays to determine the presence of pathogenic SNPs that might increase the risks of cancers among them. Five different in silico tools, SIFT, PROVEAN, Poly-Phen-2, Condel, and PANTHER, were used to predict and assess the functional impacts of the SNPs. Out of the 80 cancer-related nsSNPs from the GWAS dataset, 52 nsSNPs were found among the Orang Asli and Malays. They were further analyzed using the bioinformatic pipeline to identify the pathogenic variants. Three nsSNPs; rs1126809 (TYR), rs10936600 (LRRC34), and rs757978 (FARP2), were found as the most damaging cancer pathogenic variants. These mutations alter the protein interface and change the allosteric sites of the respective proteins. As TYR, LRRC34, and FARP2 genes play important roles in numerous cellular processes such as cell proliferation, differentiation, growth, and cell survival; therefore, any impairment on the protein function could be involved in the development of cancer. rs1126809, rs10936600, and rs757978 are the important pathogenic variants that increase the risks of cancers among the Orang Asli and Malays. The roles and impacts of these variants in cancers will require further investigations using in vitro cancer models.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  6. Serotonergic receptor gene polymorphism and response to selective serotonin reuptake inhibitors in ethnic Malay patients with first episode of major depressive disorder
    Badamasi IM, Lye MS, Ibrahim N, Abdul Razaq NA, Ling KH, Stanslas J
    Pharmacogenomics J, 2021 Aug;21(4):498-509.
    PMID: 33731884 DOI: 10.1038/s41397-021-00228-6
    The polymorphisms of the 5HTR1A and 5HTR2A receptor genes (rs6295C/G and rs6311G/A) have been evaluated for association with SSRI treatment outcome in various populations with different results. The present study was carried out to determine the association between genotypes of HTR1A-rs6295 and HTR2A-rs6311 with SSRI treatment outcome among the ethnic Malay patients diagnosed with first-episode major depressive disorder (MDD). The patients were recruited from four tertiary hospitals in the Klang Valley region of Malaysia. Predefined efficacy phenotypes based on 25% (partial early response) and 50% (clinical efficacy response) reduction in Montgomery Asberg Depression Rating Scale-self Rated score (MADRS-S) were adopted for assessment of treatment efficacy in this study. Self-reporting for adverse effects (AE) was documented using the Patient Rated Inventory of Side Effect (PRISE) after treatment with SSRI for up to 6 weeks. Adjusted binary logistic regression between genotypes of the polymorphism obtained using sequencing technique with the treatment outcome phenotypes was performed. The 142 patients recruited were made up of 96 females (67.6%) and 46 males (32.4%). Clinical efficacy and Partial early response phenotypes were not significantly associated with genotypes of HTR1A and HTR2A polymorphism. The GG genotype of HTR2A polymorphism has decreased odds for dizziness (CNS) and increased odds for poor concentration. The GA genotype increases the odd for excessive sweating, diarrhoea, constipation and blurred vision. The CC genotype of HTR1A-rs6295 decreases the odd for nausea/vomiting and increases the odd for anxiety. Thus, some genotypes of HTR1A and HTR2A polymorphism were associated with SSRI treatment outcomes in ethnic Malay MDD patients.
    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics*
  7. Fulltext Loss-of-function HSD17B13 variants, non-alcoholic steatohepatitis and adverse liver outcomes: Results from a multi-ethnic Asian cohort
    Ting YW, Kong AS, Zain SM, Chan WK, Tan HL, Mohamed Z, et al.
    Clin Mol Hepatol, 2021 Jul;27(3):486-498.
    PMID: 33618508 DOI: 10.3350/cmh.2020.0162
    BACKGROUND/AIMS: 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients.

    METHODS: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded.

    RESULTS: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P<0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR], 0.004; 95% confidence interval [CI], 0.00-0.64; P=0.033 and HR, 0.01; 95% CI, 0.00-0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese.

    CONCLUSION: HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.

    Matched MeSH terms: Polymorphism, Single Nucleotide
  8. The utility of the Laplace effect size prior distribution in Bayesian fine-mapping studies
    Walters K, Cox A, Yaacob H
    Genet Epidemiol, 2021 Jun;45(4):386-401.
    PMID: 33410201 DOI: 10.1002/gepi.22375
    The Gaussian distribution is usually the default causal single-nucleotide polymorphism (SNP) effect size prior in Bayesian population-based fine-mapping association studies, but a recent study showed that the heavier-tailed Laplace prior distribution provided a better fit to breast cancer top hits identified in genome-wide association studies. We investigate the utility of the Laplace prior as an effect size prior in univariate fine-mapping studies. We consider ranking SNPs using Bayes factors and other summaries of the effect size posterior distribution, the effect of prior choice on credible set size based on the posterior probability of causality, and on the noteworthiness of SNPs in univariate analyses. Across a wide range of fine-mapping scenarios the Laplace prior generally leads to larger 90% credible sets than the Gaussian prior. These larger credible sets for the Laplace prior are due to relatively high prior mass around zero which can yield many noncausal SNPs with relatively large Bayes factors. If using conventional credible sets, the Gaussian prior generally yields a better trade off between including the causal SNP with high probability and keeping the set size reasonable. Interestingly when using the less well utilised measure of noteworthiness, the Laplace prior performs well, leading to causal SNPs being declared noteworthy with high probability, whilst generally declaring fewer than 5% of noncausal SNPs as being noteworthy. In contrast, the Gaussian prior leads to the causal SNP being declared noteworthy with very low probability.
    Matched MeSH terms: Polymorphism, Single Nucleotide
  9. Maximum likelihood parentage assignment using quantitative genotypes
    Hamilton MG
    Heredity (Edinb), 2021 06;126(6):884-895.
    PMID: 33692533 DOI: 10.1038/s41437-021-00421-0
    The cost of parentage assignment precludes its application in many selective breeding programmes and molecular ecology studies, and/or limits the circumstances or number of individuals to which it is applied. Pooling samples from more than one individual, and using appropriate genetic markers and algorithms to determine parental contributions to pools, is one means of reducing the cost of parentage assignment. This paper describes and validates a novel maximum likelihood (ML) parentage-assignment method, that can be used to accurately assign parentage to pooled samples of multiple individuals-previously published ML methods are applicable to samples of single individuals only-using low-density single nucleotide polymorphism (SNP) 'quantitative' (also referred to as 'continuous') genotype data. It is demonstrated with simulated data that, when applied to pools, this 'quantitative maximum likelihood' method assigns parentage with greater accuracy than established maximum likelihood parentage-assignment approaches, which rely on accurate discrete genotype calls; exclusion methods; and estimating parental contributions to pools by solving the weighted least squares problem. Quantitative maximum likelihood can be applied to pools generated using either a 'pooling-for-individual-parentage-assignment' approach, whereby each individual in a pool is tagged or traceable and from a known and mutually exclusive set of possible parents; or a 'pooling-by-phenotype' approach, whereby individuals of the same, or similar, phenotype/s are pooled. Although computationally intensive when applied to large pools, quantitative maximum likelihood has the potential to substantially reduce the cost of parentage assignment, even if applied to pools comprised of few individuals.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  10. Fulltext Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer
    Karunamuni RA, Huynh-Le MP, Fan CC, Thompson W, Eeles RA, Kote-Jarai Z, et al.
    Prostate Cancer Prostatic Dis, 2021 Jun;24(2):532-541.
    PMID: 33420416 DOI: 10.1038/s41391-020-00311-2
    BACKGROUND: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).

    MATERIALS AND METHOD: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.

    RESULTS: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.

    CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

    Matched MeSH terms: Polymorphism, Single Nucleotide*
  11. Fulltext Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3
    Mocci E, Kundu P, Wheeler W, Arslan AA, Beane-Freeman LE, Bracci PM, et al.
    Cancer Res, 2021 Jun 01;81(11):3134-3143.
    PMID: 33574088 DOI: 10.1158/0008-5472.CAN-20-3267
    Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 × 10-8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, P interaction = 3.08 × 10-9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r 2 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. SIGNIFICANCE: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  12. Fulltext Gene Polymorphisms of the Renin-Angiotensin-Aldosterone System as Risk Factors for the Development of In-Stent Restenosis in Patients with Stable Coronary Artery Disease
    Azova M, Timizheva K, Ait Aissa A, Blagonravov M, Gigani O, Aghajanyan A, et al.
    Biomolecules, 2021 05 20;11(5).
    PMID: 34065198 DOI: 10.3390/biom11050763
    This study investigated the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms as possible genetic risk factors for the restenosis development in patients with drug-eluting stents. 113 participants had coronary artery disease and underwent stenting. The control group consisted of 62 individuals with intact coronary arteries. Patients were divided into two groups: with in-stent restenosis (ISR) and without it. The patients with ISR were classified into subgroups by the terms of the restenosis development and age. Real-time PCR and Restriction Fragment Length Polymorphism-PCR were used to genotype the study participants for RAAS gene polymorphisms. We found that the development of restenosis is generally associated with the minor A allele for renin (REN) rs2368564 and the major TT genotype for angiotensinogen (AGT) rs699. The heterozygous genotype for AGT rs4762 acts as a protective marker. A minor A allele for angiotensin II type 2 receptor (AGTR2) rs1403543 is associated with a risk of restenosis in people under 65 years old. Among patients with the early ISR, heterozygotes for angiotensin II type 1 receptor (AGTR1) rs5186 are more frequent, as well as A allele carriers for AGTR2 rs1403543. A minor homozygous genotype for REN rs41317140 and heterozygous genotype for aldosterone synthase (CYP11B2) rs1799998 are predisposed to the late restenosis. Thus, to choose the effective treatment tactics for patients with coronary artery disease, it is necessary to genotype patients for the RAAS polymorphisms, which, along with age and clinical characteristics, will allow a comprehensive assessment of the risk of the restenosis development after stenting.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  13. Fulltext Predictive SNPs for β0-thalassemia/HbE disease severity
    Munkongdee T, Tongsima S, Ngamphiw C, Wangkumhang P, Peerapittayamongkol C, Hashim HB, et al.
    Sci Rep, 2021 05 14;11(1):10352.
    PMID: 33990643 DOI: 10.1038/s41598-021-89641-2
    β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β0-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β0-thalassemia/HbE population.
    Matched MeSH terms: Polymorphism, Single Nucleotide
  14. BsmI-ApaI-TaqI TAC (BAt) Haplotype of Vitamin D Receptor Gene Is Associated with Increased Risk of Major Depressive Disorder
    Lye MS, Tor YS, Tey YY, Shahabudin A, Loh SP, Ibrahim N, et al.
    J Mol Neurosci, 2021 May;71(5):981-990.
    PMID: 33034825 DOI: 10.1007/s12031-020-01719-0
    Heritability of major depressive disorder (MDD) is between 36 and 44%, suggesting that up to nearly half of the phenotypic variability is attributable to genes. A number of genetic polymorphisms have been shown to predispose certain individuals to depression. Of particular interest are the polymorphisms of the vitamin D receptor (VDR) gene. Although the VDR gene has been well characterized and a vast number of polymorphisms have been identified, the association between BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) single-nucleotide polymorphisms (SNPs), together with their haplotypes, and MDD risk have yet to be established. We conducted a matched case-control study with a total of 600 participants comprising 300 major depressive disorder (MDD) cases and 300 controls matched by age, gender and ethnicity in a 1:1 ratio, in four public hospitals in Kuala Lumpur and Selangor. Three adjacent SNPs of the VDR gene-BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236)-were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios and 95% confidence intervals (CIs) were obtained from conditional logistic regression using Stata 16. Linkage disequilibrium and haplotype association with MDD were analyzed using the online SNPStats program. None of the genotypes of the three SNPs was significantly associated with risk of developing MDD after adjusting for confounding factors. However, the TAC (BAt) haplotype was associated with increased odds of MDD (adjusted OR = 2.17, 95% CI = 1.30-3.61, p = 0.003) using CCT (baT) as reference haplotype. The findings suggest that the BsmI-ApaI-TaqI TAC (BAt) haplotype of the VDR gene increases susceptibility to MDD.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  15. Fulltext The Role of Genetic Polymorphism and Other Factors on Clopidogrel Resistance (CR) in an Asian Population with Coronary Heart Disease (CHD)
    Akkaif MA, Daud NAA, Sha'aban A, Ng ML, Abdul Kader MAS, Noor DAM, et al.
    Molecules, 2021 Apr 01;26(7).
    PMID: 33915807 DOI: 10.3390/molecules26071987
    Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2-81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  16. Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians
    Wang CW, Tassaneeyakul W, Chen CB, Chen WT, Teng YC, Huang CY, et al.
    J Allergy Clin Immunol, 2021 04;147(4):1402-1412.
    PMID: 32791162 DOI: 10.1016/j.jaci.2020.08.003
    BACKGROUND: Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole-induced SCAR remains unclear.

    OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR.

    METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia.

    RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1).

    CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.

    Matched MeSH terms: Polymorphism, Single Nucleotide
  17. Fulltext Genetic Association of CYP1B1 4326 C>G Polymorphism with Disease-Free Survival in TNBC Patients Undergoing TAC Chemotherapy Regimen
    Abdul Aziz AA, Md Salleh MS, Yahya MM, Zakaria AD, Ankathil R
    Asian Pac J Cancer Prev, 2021 Apr 01;22(4):1319-1324.
    PMID: 33906328 DOI: 10.31557/APJCP.2021.22.4.1319
    BACKGROUND: Triple negative breast cancer (TNBC) which is treated with taxane, adriamycin and cyclophosphamide (TAC) chemotherapy regimen show variation in treatment response. CYP1B1 4326 C>G polymorphism has been implicated in contributing to the differences in treatment response in various types of cancers.

    AIM: The objective of the present study was to investigate whether this polymorphism modulate the risk of disease recurrence in TNBC patients undergoing TAC chemotherapy regimen.

    METHODS: Blood samples of 76 immunohistochemistry confirmed TNBC patients were recruited. The genotyping of CYP1B1 4326 C>G polymorphism was carried out using PCR-RFLP technique. The genotype patterns were categorized into homozygous wildtype, heterozygous and homozygous variant. Kaplan-Meier analysis followed by Cox proportional hazard regression model were performed to evaluate the TNBC patients' recurrence risk.

    RESULTS: Out of 76 TNBC patients, 25 (33.0%) showed disease recurrence after one-year evaluation. Kaplan Meier analysis showed that TNBC patients who are carriers of CYP1B1 4326 GG variant genotypes (37.0%) had a significantly lower probability of disease-free rates as compared to TNBC patients who are carriers of CYP1B1 4326 CC/CG genotypes (71.0%). Univariate and multivariate Cox analysis demonstrated that TNBC patients who carried CYP1B1 4326 GG variant genotype had a significantly higher risk of recurrence with HR: 2.50 and HR: 4.18 respectively, even after adjustment as compared to TNBC patients who were carriers of CYP1B1 4326 CC and CG genotypes.

    CONCLUSION: Our results demonstrate the potential use of CYP1B1 4325 GG variant genotype as a candidate biomarker in predicting risk of recurrence in TNBC patients undergoing TAC chemotherapy regimen.

    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics*
  18. Fulltext The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease
    Nakasone R, Ashina M, Abe S, Tanimura K, Van Rostenberghe H, Fujioka K
    Int J Environ Res Public Health, 2021 03 29;18(7).
    PMID: 33805292 DOI: 10.3390/ijerph18073520
    Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the HMOX1 gene, (GT)n repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on HMOX1 polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT)n repeats based on transcriptional capacity should be further investigated.
    Matched MeSH terms: Polymorphism, Single Nucleotide
  19. Fulltext The Unique Biology behind the Early Onset of Breast Cancer
    Siddig A, Tengku Din TADA, Mohd Nafi SN, Yahya MM, Sulong S, Wan Abdul Rahman WF
    Genes (Basel), 2021 03 05;12(3).
    PMID: 33807872 DOI: 10.3390/genes12030372
    Breast cancer commonly affects women of older age; however, in developing countries, up to 20% of breast cancer cases present in young women (younger than 40 years as defined by oncology literature). Breast cancer in young women is often defined to be aggressive in nature, usually of high histological grade at the time of diagnosis and negative for endocrine receptors with poor overall survival rate. Several researchers have attributed this aggressive nature to a hidden unique biology. However, findings in this aspect remain controversial. Thus, in this article, we aimed to review published work addressing somatic mutations, chromosome copy number variants, single nucleotide polymorphisms, differential gene expression, microRNAs and gene methylation profile of early-onset breast cancer, as well as its altered pathways resulting from those aberrations. Distinct biology behind early-onset of breast cancer was clear among estrogen receptor-positive and sporadic cases. However, further research is needed to determine and validate specific novel markers, which may help in customizing therapy for this group of patients.
    Matched MeSH terms: Polymorphism, Single Nucleotide
  20. Fulltext A Linkage-Based Genome Assembly for the Mosquito Aedes albopictus and Identification of Chromosomal Regions Affecting Diapause
    Boyle JH, Rastas PMA, Huang X, Garner AG, Vythilingam I, Armbruster PA
    Insects, 2021 Feb 16;12(2).
    PMID: 33669192 DOI: 10.3390/insects12020167
    The Asian tiger mosquito, Aedes albopictus, is an invasive vector mosquito of substantial public health concern. The large genome size (~1.19-1.28 Gb by cytofluorometric estimates), comprised of ~68% repetitive DNA sequences, has made it difficult to produce a high-quality genome assembly for this species. We constructed a high-density linkage map for Ae. albopictus based on 111,328 informative SNPs obtained by RNAseq. We then performed a linkage-map anchored reassembly of AalbF2, the genome assembly produced by Palatini et al. (2020). Our reassembled genome sequence, AalbF3, represents several improvements relative to AalbF2. First, the size of the AalbF3 assembly is 1.45 Gb, almost half the size of AalbF2. Furthermore, relative to AalbF2, AalbF3 contains a higher proportion of complete and single-copy BUSCO genes (84.3%) and a higher proportion of aligned RNAseq reads that map concordantly to a single location of the genome (46%). We demonstrate the utility of AalbF3 by using it as a reference for a bulk-segregant-based comparative genomics analysis that identifies chromosomal regions with clusters of candidate SNPs putatively associated with photoperiodic diapause, a crucial ecological adaptation underpinning the rapid range expansion and climatic adaptation of A. albopictus.
    Matched MeSH terms: Polymorphism, Single Nucleotide
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links