Displaying publications 1 - 20 of 141 in total

Abstract:
Sort:
  1. Fulltext The schizophrenia genetics knowledgebase: a comprehensive update of findings from candidate gene studies
    Liu C, Kanazawa T, Tian Y, Mohamed Saini S, Mancuso S, Mostaid MS, et al.
    Transl Psychiatry, 2019 08 27;9(1):205.
    PMID: 31455759 DOI: 10.1038/s41398-019-0532-4
    Over 3000 candidate gene association studies have been performed to elucidate the genetic underpinnings of schizophrenia. However, a comprehensive evaluation of these studies' findings has not been undertaken since the decommissioning of the schizophrenia gene (SzGene) database in 2011. As such, we systematically identified and carried out random-effects meta-analyses for all polymorphisms with four or more independent studies in schizophrenia along with a series of expanded meta-analyses incorporating published and unpublished genome-wide association (GWA) study data. Based on 550 meta-analyses, 11 SNPs in eight linkage disequilibrium (LD) independent loci showed Bonferroni-significant associations with schizophrenia. Expanded meta-analyses identified an additional 10 SNPs, for a total of 21 Bonferroni-significant SNPs in 14 LD-independent loci. Three of these loci (MTHFR, DAOA, ARVCF) had never been implicated by a schizophrenia GWA study. In sum, the present study has provided a comprehensive summary of the current schizophrenia genetics knowledgebase and has made available all the collected data as a resource for the research community.
    Matched MeSH terms: Genetic Association Studies
  2. Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population
    Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung WH, et al.
    Pharmacogenomics J, 2017 03;17(2):170-173.
    PMID: 26927288 DOI: 10.1038/tpj.2016.10
    Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.
    Matched MeSH terms: Genetic Association Studies
  3. A New Zealand platform to enable genetic investigation of adverse drug reactions
    Maggo SD, Chua EW, Chin P, Cree S, Pearson J, Doogue M, et al.
    N Z Med J, 2017 Dec 01;130(1466):62-69.
    PMID: 29197902
    A multitude of factors can affect drug response in individuals. It is now well established that variations in genes, especially those coding for drug metabolising enzymes, can alter the pharmacokinetic and/or pharmacodynamic profile of a drug, impacting on efficacy and often resulting in drug-induced toxicity. The UDRUGS study is an initiative from the Carney Centre for Pharmacogenomics to biobank DNA and store associated clinical data from patients who have suffered rare and/or serious adverse drug reactions (ADRs). The aim is to provide a genetic explanation of drug-induced ADRs using methods ranging from Sanger sequencing to whole exome and whole genome sequencing. Participants for the UDRUGS study are recruited from various sources, mainly via referral through clinicians working in Canterbury District Health Board, but also from district health boards across New Zealand. Participants have also self-referred to us from word-of-mouth communication between participants. We have recruited various ADRs across most drug classes. Where possible, we have conducted genetic analyses in single or a cohort of cases to identify known and novel genetic association(s) to offer an explanation to why the ADR occurred. Any genetic results relevant to the ADR are communicated back to the referring clinician and/or participant. In conclusion, we have developed a programme for studying the genetic basis of severe, rare or unusual ADR cases resulting from pharmacological treatment. Genomic analyses could eventually identify most genetic variants that predispose to ADRs, enabling a priori detection of such variants with high throughput DNA tests.
    Matched MeSH terms: Genetic Association Studies/methods
  4. Fulltext Association of copy number variations in complement factor H-Related genes among age-related macular degenerative subjects
    Bakri NM, Ramachandran V, Kee HF, Subrayan V, Isa H, Ngah NF, et al.
    Kaohsiung J. Med. Sci., 2017 Dec;33(12):602-608.
    PMID: 29132549 DOI: 10.1016/j.kjms.2017.08.003
    Age-related macular degeneration (AMD) is the most widely recognised cause of irreversible vision loss and previous studies have suggested that the advancement of wet AMD is influenced by both modifiable and non-modifiable elements. Single nucleotide polymorphism (SNPs) and copy number of variations (CNVs) have been associated with AMD in various populations, however the results are conflicting. Our aim is to determine the CNVs of Complement Factor H-Related genes among Malaysian subjects with wet AMD. 130 patients with wet AMD and 120 healthy controls were included in this research. DNA was extracted from all subjects and CNVs of CFH, CFHR1 and CFHR3 genes; determined using quantitative real-time PCR and were compared between the two groups. A consistent association was observed between CFH gene and wet AMD susceptibility (P 
    Matched MeSH terms: Genetic Association Studies*
  5. Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance
    Saunus JM, Quinn MC, Patch AM, Pearson JV, Bailey PJ, Nones K, et al.
    J Pathol, 2015 Nov;237(3):363-78.
    PMID: 26172396 DOI: 10.1002/path.4583
    Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting HER3, which is broadly over-expressed and activated in BMs, independent of primary site and systemic therapy.
    Matched MeSH terms: Genetic Association Studies
  6. Fulltext The Association of Estrogen Receptor-β Gene Variation With Salt-Sensitive Blood Pressure
    Manosroi W, Tan JW, Rariy CM, Sun B, Goodarzi MO, Saxena AR, et al.
    J Clin Endocrinol Metab, 2017 11 01;102(11):4124-4135.
    PMID: 28938457 DOI: 10.1210/jc.2017-00957
    Context: Hypertension in young women is uncommon compared with young men and older women. Estrogen appears to protect most women against hypertension, with incidence increasing after menopause. Because some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle.

    Objective: To determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.

    Methods: Candidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (<51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.

    Results: Multivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.

    Conclusions: The variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.

    Matched MeSH terms: Genetic Association Studies
  7. Fulltext Clinical and genetic differences between pustular psoriasis subtypes
    Twelves S, Mostafa A, Dand N, Burri E, Farkas K, Wilson R, et al.
    J Allergy Clin Immunol, 2019 03;143(3):1021-1026.
    PMID: 30036598 DOI: 10.1016/j.jaci.2018.06.038
    BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations.

    OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort.

    METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases.

    RESULTS: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P 

    Matched MeSH terms: Genetic Association Studies
  8. Fulltext GABRG2 rs211037 polymorphism and epilepsy: a systematic review and meta-analysis
    Haerian BS, Baum L
    Seizure, 2013 Jan;22(1):53-8.
    PMID: 23140995 DOI: 10.1016/j.seizure.2012.10.007
    PURPOSE: The gamma-aminobutyric acid A receptor, gamma 2 (GABRG2) gene encodes the GABRγ2 protein, which has been implicated in susceptibility to epilepsy. Several studies have examined a possible link between the exonic GABRG2 rs211037 locus and susceptibility to febrile seizure (FS) and idiopathic generalized epilepsy (IGE), however results have been inconclusive. We therefore performed a systematic review and meta-analysis to examine whether this polymorphism is associated with FS or IGE.
    METHODS: Eight studies comprising 1871 epilepsy patients and 1387 controls, which evaluated association of the GABRG2 rs211037 polymorphism with susceptibility to epilepsy, were included in this meta-analysis. Meta-analysis was carried out separately for FS and IGE.
    RESULTS: Meta-analysis showed a significant association between this polymorphism and susceptibility to FS in a codominant (TT vs. CC, OR 0.47, 95% CI 0.30-0.73, p=0.0008 and TT vs. CT, OR 0.59, 95% CI 0.42-0.83, p=0.003) and dominant (OR 0.54, 95% CI 0.39-0.75, p=0.0002) genetic models, influenced by two studies with small sample size. Neither allele nor genotype association was observed with IGE.
    CONCLUSION: This study showed significant association of GABRG2 rs211037 with susceptibility to FS, caused by two studies with small sample sizes, however the possibility of false positive results due to the effect of significant studies for FS cannot be excluded. Future studies with larger sample sizes of these patients are suggested to verify the results.
    Matched MeSH terms: Genetic Association Studies/statistics & numerical data
  9. Fulltext Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy
    Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.
    Seizure, 2011 Jun;20(5):387-94.
    PMID: 21316268 DOI: 10.1016/j.seizure.2011.01.008
    It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy.
    Matched MeSH terms: Genetic Association Studies/methods
  10. Association of common genetic variants with vitamin D status in Malaysian children with epilepsy
    Kong AN, Fong CY, Ng CC, Mohamed AR, Khoo TB, Ng RL, et al.
    Seizure, 2020 Jul;79:103-111.
    PMID: 32464532 DOI: 10.1016/j.seizure.2020.05.009
    PURPOSE: Children with epilepsy (CWE) are at risk of vitamin D deficiency. Single nucleotide polymorphisms (SNPs) affecting the vitamin D pathway are potentially important risk factors for serum 25-hydroxyvitamin D [25(OH)D] concentration. The aims of our study were to evaluate the association of vitamin d-related SNPs to serum 25(OH)D concentrations in Malaysian CWE.

    METHODS: Cross-sectional study of Malaysian ambulant CWE on antiseizure medication for >1 year. Sixteen SNPs in 8 genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1, CYP27A1, CYP3A4, NADSYN1/DHCR7) were genotyped. Linear and logistic regression models and co-variates adjusted analyses were used. SNPs with significant associations were further analysed in a group of ethnically-matched healthy Malaysian children.

    RESULTS: 239 CWE were recruited (52.7% Malay, 24.3% Chinese and 23.0% Indian) with mean serum 25(OH)D of 58.8 nmol/L (SD 25.7). Prevalence of vitamin D deficiency (≤37.5 nmol/L) was 23.0%. Minor allele of GC-rs4588-A was associated with lower serum 25(OH)D in the meta-analysis of both CWE (β -8.11, P = 0.002) and Malaysian healthy children (β -5.08, P < 0.001), while VDR-rs7975232-A was significantly associated with reduced odds of vitamin D deficiency in Malay subgroup of CWE (OR: 0.16; 95% CI: 0.06-0.49; P = 0.001) and this association was not found in the healthy children group.

    CONCLUSIONS: Our results suggest that GC-rs4588 is associated with lower serum 25(OH)D concentration in both Malaysian CWE and healthy children, while VDR-rs7975232A is associated with lower risk of vitamin D deficiency in Malaysian CWE of Malay ethnicity. Our findings may assist in the genetic risk stratification of low vitamin D status among CWE.

    Matched MeSH terms: Genetic Association Studies
  11. Fulltext The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis
    Au A, Griffiths LR, Cheng KK, Wee Kooi C, Irene L, Keat Wei L
    Sci Rep, 2015 Dec 15;5:18224.
    PMID: 26666837 DOI: 10.1038/srep18224
    Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95%  CI:1.11-1.58) and co-dominant models (OR = 1.24, 95%  CI:1.02-1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95%  CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke.
    Matched MeSH terms: Genetic Association Studies*
  12. Fulltext Helicobacter pylori genetic diversity and gastro-duodenal diseases in Malaysia
    Gunaletchumy SP, Seevasant I, Tan MH, Croft LJ, Mitchell HM, Goh KL, et al.
    Sci Rep, 2014 Dec 11;4:7431.
    PMID: 25503415 DOI: 10.1038/srep07431
    Helicobacter pylori infection results in diverse clinical conditions ranging from chronic gastritis and ulceration to gastric adenocarcinoma. Among the multiethnic population of Malaysia, Indians consistently have a higher H. pylori prevalence as compared with Chinese and Malays. Despite the high prevalence of H. pylori, Indians have a relatively low incidence of peptic ulcer disease and gastric cancer. In contrast, gastric cancer and peptic ulcer disease incidence is high in Chinese. H. pylori strains from Chinese strains predominantly belong to the hspEAsia subpopulation while Indian/Malay strains mainly belong to the hspIndia subpopulation. By comparing the genome of 27 Asian strains from different subpopulations, we identified six genes associated with risk of H. pylori-induced peptic ulcer disease and gastric cancer. This study serves as an important foundation for future studies aiming to understand the role of bacterial factors in H. pylori-induced gastro-duodenal diseases.
    Matched MeSH terms: Genetic Association Studies
  13. Fulltext Copy number variation in exportin-4 (XPO4) gene and its association with histological severity of non-alcoholic fatty liver disease
    Zain SM, Mohamed Z, Pirmohamed M, Tan HL, Alshawsh MA, Mahadeva S, et al.
    Sci Rep, 2015 Aug 21;5:13306.
    PMID: 26293807 DOI: 10.1038/srep13306
    A recent genome-wide copy number (CNV) scan identified a 13q12.11 duplication in the exportin-4 (XPO4) gene to be associated with non-alcoholic steatohepatitis (NASH). We sought to confirm the finding in a larger cohort and to assess the serum XPO4 pattern in a broad spectrum of non-alcoholic fatty liver disease (NAFLD) cases. We analysed 249 NAFLD patients and 232 matched controls using TaqMan assay and serum XPO4 was measured. Copy number distribution was as follows: copy number neutral (NAFLD: 53.8%, controls: 68.6%), copy number losses (NAFLD: 13.3%, controls: 12.9%), copy number gains (NAFLD: 32.9%, controls: 18.5%). CNV gain was significantly associated with a greater risk of NAFLD (adjusted OR 2.22, 95% CI 1.42-3.46, P = 0.0004) and NASH (adjusted OR 2.33, 95% CI 1.47-3.68, P = 0.0003). Interestingly, subjects carrying extra copy number showed significantly higher serum ALT and triglyceride (P 
    Matched MeSH terms: Genetic Association Studies*
  14. Fulltext Characterizing haploinsufficiency of SHELL gene to improve fruit form prediction in introgressive hybrids of oil palm
    Teh CK, Muaz SD, Tangaya P, Fong PY, Ong AL, Mayes S, et al.
    Sci Rep, 2017 06 08;7(1):3118.
    PMID: 28596562 DOI: 10.1038/s41598-017-03225-7
    The fundamental trait in selective breeding of oil palm (Eleais guineensis Jacq.) is the shell thickness surrounding the kernel. The monogenic shell thickness is inversely correlated to mesocarp thickness, where the crude palm oil accumulates. Commercial thin-shelled tenera derived from thick-shelled dura × shell-less pisifera generally contain 30% higher oil per bunch. Two mutations, sh MPOB (M1) and sh AVROS (M2) in the SHELL gene - a type II MADS-box transcription factor mainly present in AVROS and Nigerian origins, were reported to be responsible for different fruit forms. In this study, we have tested 1,339 samples maintained in Sime Darby Plantation using both mutations. Five genotype-phenotype discrepancies and eight controls were then re-tested with all five reported mutations (sh AVROS , sh MPOB , sh MPOB2 , sh MPOB3 and sh MPOB4 ) within the same gene. The integration of genotypic data, pedigree records and shell formation model further explained the haploinsufficiency effect on the SHELL gene with different number of functional copies. Some rare mutations were also identified, suggesting a need to further confirm the existence of cis-compound mutations in the gene. With this, the prediction accuracy of fruit forms can be further improved, especially in introgressive hybrids of oil palm. Understanding causative variant segregation is extremely important, even for monogenic traits such as shell thickness in oil palm.
    Matched MeSH terms: Genetic Association Studies
  15. 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: Genetic Association Studies
  16. Fulltext Key glycolytic branch influences mesocarp oil content in oil palm
    Ruzlan N, Low YSJ, Win W, Azizah Musa N, Ong AL, Chew FT, et al.
    Sci Rep, 2017 Aug 29;7(1):9626.
    PMID: 28852058 DOI: 10.1038/s41598-017-10195-3
    The fructose-1,6-bisphosphate aldolase catalyzed glycolysis branch that forms dihydroxyacetone phosphate and glyceraldehyde-3-phosphate was identified as a key driver of increased oil synthesis in oil palm and was validated in Saccharomyces cerevisiae. Reduction in triose phosphate isomerase (TPI) activity in a yeast knockdown mutant resulted in 19% increase in lipid content, while yeast strains overexpressing oil palm fructose-1,6-bisphosphate aldolase (EgFBA) and glycerol-3-phosphate dehydrogenase (EgG3PDH) showed increased lipid content by 16% and 21%, respectively. Genetic association analysis on oil palm SNPs of EgTPI SD_SNP_000035801 and EgGAPDH SD_SNP_000041011 showed that palms harboring homozygous GG in EgTPI and heterozygous AG in EgGAPDH exhibited higher mesocarp oil content based on dry weight. In addition, AG genotype of the SNP of EgG3PDH SD_SNP_000008411 was associated with higher mean mesocarp oil content, whereas GG genotype of the EgFBA SNP SD_SNP_000007765 was favourable. Additive effects were observed with a combination of favourable alleles in TPI and FBA in Nigerian x AVROS population (family F7) with highest allele frequency GG.GG being associated with a mean increase of 3.77% (p value = 2.3E-16) oil content over the Family 1. An analogous effect was observed in yeast, where overexpressed EgFBA in TPI - resulted in a 30% oil increment. These results provide insights into flux balances in glycolysis leading to higher yield in mesocarp oil-producing fruit.
    Matched MeSH terms: Genetic Association Studies
  17. Fulltext Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis
    Leong SL, Chaiyakunapruk N, Lee SW
    Sci Rep, 2017 02 27;7(1):39.
    PMID: 28232737 DOI: 10.1038/s41598-017-00075-1
    Anthracyclines play an important role in the management of patients with cancer but the development of anthracycline-induced cardiotoxicity (ACT) remains a significant concern for most clinicians. Recently, genetic approach has been used to identify patients at increased risk of ACT. This systematic review assessed the association between genomic markers and ACT. A systematic literature search was performed in Medline, PubMed, Cochrane Central Register of Controlled Studies, CINAHL Plus, AMED, EMBASE and HuGE Navigator from inception until May 2016. Twenty-eight studies examining the association of genetic variants and ACT were identified. These studies examined 84 different genes and 147 single nucleotide polymorphisms. Meta-analyses showed 3 risk variants significantly increased the risk for ACT; namely ABCC2 rs8187710 (pooled odds ratio: 2.20; 95% CI: 1.36-3.54), CYBA rs4673 (1.55; 1.05-2.30) and RAC2 rs13058338 (1.79; 1.27-2.52). The current evidence remains unclear on the potential role of pharmacogenomic screening prior to anthracycline therapy. Further research is needed to improve the diagnostic and prognostic role in predicting ACT.
    Matched MeSH terms: Genetic Association Studies*
  18. Analysis of peptidyl-propyl-cis/trans isomerase 1 (PIN1) gene -842(G > C) and -667(T > C) polymorphic variants in relation to breast cancer risk and clinico-pathological parameters
    Naidu R, Har YC, Taib NA
    Scand J Clin Lab Invest, 2011 Oct;71(6):500-6.
    PMID: 21745146 DOI: 10.3109/00365513.2011.590223
    The purpose of this study was to investigate the association between the peptidyl-propyl-cis/trans isomerase 1 (PIN1) -842(G > C) and -667(T > C) polymorphic variants and breast cancer risk among Malaysian ethnic groups namely the Malays, Chinese and Indians, as well as clinico-pathological characteristics of the patients.
    Matched MeSH terms: Genetic Association Studies
  19. Complement components 2 and 7 (C2 and C7) gene polymorphisms are not major risk factors for SLE susceptibility in the Malaysian population
    Lian LH, Ching AS, Chong ZY, Chua KH
    Rheumatol Int, 2012 Nov;32(11):3665-8.
    PMID: 21881993 DOI: 10.1007/s00296-011-2070-0
    There have been numerous studies linking complement components and the pathogenesis of systemic lupus erythematosus (SLE). This is due to their numerous roles in modulating immune responses in the human body. This study examined the association of C2 and C7 genetic polymorphisms with the susceptibility to SLE based on two separate cohorts of patient and control samples from Malaysia. The 28-bp deletion in the C2 exon-intron junction and single nucleotide polymorphism in the 3'untranslated region in the C7 genes were detected based on direct polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively. A total of 150 patient and 150 healthy control samples were screened, but there was no association detected between either genes. All individuals presented with null deletion in C2 genes, while the C allele and CC genotypes were most commonly scored. These overall results suggest a lack of strong association with the C2 and C7 gene polymorphisms to the susceptibility of SLE in the Malaysian population.
    Matched MeSH terms: Genetic Association Studies
  20. Meta-analysis of polymorphisms in TPH2 gene and suicidal behavior
    Choong MY, Tee SF, Tang PY
    Psychiatry Res, 2014 Dec 30;220(3):1163-6.
    PMID: 25219619 DOI: 10.1016/j.psychres.2014.07.076
    Matched MeSH terms: Genetic Association Studies
Related Terms
Filters
Contact Us

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

External Links