Displaying publications 21 - 40 of 83 in total

Abstract:
Sort:
  1. Fulltext Association of ESR1 Germline Variants with TP53 Somatic Variants in Breast Tumors in a Genome-wide Study
    Tjader NP, Beer AJ, Ramroop J, Tai MC, Ping J, Gandhi T, et al.
    Cancer Res Commun, 2024 Jun 27;4(6):1597-1608.
    PMID: 38836758 DOI: 10.1158/2767-9764.CRC-24-0026
    In breast tumors, somatic mutation frequencies in TP53 and PIK3CA vary by tumor subtype and ancestry. Emerging data suggest tumor mutation status is associated with germline variants and genetic ancestry. We aimed to identify germline variants that are associated with somatic TP53 or PIK3CA mutation status in breast tumors. A genome-wide association study was conducted in 2,850 women of European ancestry with breast cancer using TP53 and PIK3CA mutation status (positive or negative) as well as specific functional categories [e.g., TP53 gain-of-function (GOF) and loss-of-function, PIK3CA activating] as phenotypes. Germline variants showing evidence of association were selected for validation analyses and tested in multiple independent datasets. Discovery association analyses found five variants associated with TP53 mutation status with P values <1 × 10-6 and 33 variants with P values <1 × 10-5. Forty-four variants were associated with PIK3CA mutation status with P values <1 × 10-5. In validation analyses, only variants at the ESR1 locus were associated with TP53 mutation status after multiple comparisons corrections. Combined analyses in European and Malaysian populations found ESR1 locus variants rs9383938 and rs9479090 associated with the presence of TP53 mutations overall (P values 2 × 10-11 and 4.6 × 10-10, respectively). rs9383938 also showed association with TP53 GOF mutations (P value 6.1 × 10-7). rs9479090 showed suggestive evidence (P value 0.02) for association with TP53 mutation status in African ancestry populations. No other variants were significantly associated with TP53 or PIK3CA mutation status. Larger studies are needed to confirm these findings and determine if additional variants contribute to ancestry-specific differences in mutation frequency.

    SIGNIFICANCE: Emerging data show ancestry-specific differences in TP53 and PIK3CA mutation frequency in breast tumors suggesting that germline variants may influence somatic mutational processes. This study identified variants near ESR1 associated with TP53 mutation status and identified additional loci with suggestive association which may provide biological insight into observed differences.

    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  2. Association between genetic polymorphisms in interferon regulatory factor 5 (IRF5) gene and Malaysian patients with Crohn's disease
    Chua KH, Lian LH, Khor WC, Lee WS, Hilmi I, Goh KL, et al.
    J Dig Dis, 2015 Apr;16(4):205-16.
    PMID: 25564941 DOI: 10.1111/1751-2980.12229
    The study aimed to investigate the association between the interferon regulatory factor 5 (IRF5) gene polymorphisms and the onset of Crohn's disease (CD) in a Malaysian cohort.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  3. Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy
    Azize NA, Ngah WZ, Othman Z, Md Desa N, Chin CB, Md Yunus Z, et al.
    J Hum Genet, 2014 Nov;59(11):593-7.
    PMID: 25231368 DOI: 10.1038/jhg.2014.69
    Glycine encephalopathy (GCE) or nonketotic hyperglycinemia is an inborn error of glycine metabolism, inherited in an autosomal recessive manner due to a defect in any one of the four enzymes aminomethyltransferase (AMT), glycine decarboxylase (GLDC), glycine cleavage system protein-H (GCSH) and dehydrolipoamide dehydrogenase in the glycine cleavage system. This defect leads to glycine accumulation in body tissues, including the brain, and causes various neurological symptoms such as encephalopathy, hypotonia, apnea, intractable seizures and possible death. We screened 14 patients from 13 families with clinical and biochemical features suggestive of GCE for mutation in AMT, GLDC and GCSH genes by direct sequencing and genomic rearrangement of GLDC gene using a multiplex ligation-dependant probe amplification. We identified mutations in all 14 patients. Seven patients (50%) have biallelic mutations in GLDC gene, six patients (43%) have biallelic mutations in AMT gene and one patient (7%) has mutation identified in only one allele in GLDC gene. Majority of the mutations in GLDC and AMT were missense mutations and family specific. Interestingly, two mutations p.Arg265His in AMT gene and p.His651Arg in GLDC gene occurred in the Penan sub-population. No mutation was found in GCSH gene. We concluded that mutations in both GLDC and AMT genes are the main cause of GCE in Malaysian population.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  4. Fulltext Functional analyses of C.2268dup in thyroid peroxidase gene associated with goitrous congenital hypothyroidism
    Lee CC, Harun F, Jalaludin MY, Lim CY, Ng KL, Mat Junit S
    Biomed Res Int, 2014;2014:370538.
    PMID: 24745015 DOI: 10.1155/2014/370538
    The c.2268dup mutation in thyroid peroxidase (TPO) gene was reported to be a founder mutation in Taiwanese patients with dyshormonogenetic congenital hypothyroidism (CH). The functional impact of the mutation is not well documented. In this study, homozygous c.2268dup mutation was detected in two Malaysian-Chinese sisters with goitrous CH. Normal and alternatively spliced TPO mRNA transcripts were present in thyroid tissues of the two sisters. The abnormal transcript contained 34 nucleotides originating from intron 12. The c.2268dup is predicted to generate a premature termination codon (PTC) at position 757 (p.Glu757X). Instead of restoring the normal reading frame, the alternatively spliced transcript has led to another stop codon at position 740 (p.Asp739ValfsX740). The two PTCs are located at 116 and 201 nucleotides upstream of the exons 13/14 junction fulfilling the requirement for a nonsense-mediated mRNA decay (NMD). Quantitative RT-PCR revealed an abundance of unidentified transcripts believed to be associated with the NMD. TPO enzyme activity was not detected in both patients, even though a faint TPO band of about 80 kD was present. In conclusion, the c.2268dup mutation leads to the formation of normal and alternatively spliced TPO mRNA transcripts with a consequential loss of TPO enzymatic activity in Malaysian-Chinese patients with goitrous CH.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  5. HLA-DRA rs3129882 A/G polymorphism was not a risk factor for Parkinson's disease in Chinese-based populations: a meta-analysis
    Ma ZG, Liu TW, Bo YL
    Int J Neurosci, 2015 Apr;125(4):241-6.
    PMID: 24849299 DOI: 10.3109/00207454.2014.926349
    Many studies have evaluated the association between the HLA-DRA rs3129882 A/G polymorphism and risk for Parkinson's disease (PD) in Chinese-based populations, however, published data remain inconclusive. Therefore, we performed a meta-analysis from all relevant studies to evaluate an association of HLA-DRA rs3129882 A/G polymorphism with susceptibility to PD.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  6. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays
    Apalasamy YD, Ming MF, Rampal S, Bulgiba A, Mohamed Z
    Braz. J. Med. Biol. Res., 2012 Dec;45(12):1119-26.
    PMID: 22911346
    The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  7. Fulltext A replication study confirms the association of dendritic cell immunoreceptor (DCIR) polymorphisms with ACPA - negative RA in a large Asian cohort
    Guo J, Wu X, Too CL, Yin F, Lu X, He J, et al.
    PLoS One, 2012;7(7):e41228.
    PMID: 22829930 DOI: 10.1371/journal.pone.0041228
    OBJECTIVES: Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.

    METHODS: We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.

    RESULTS: DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall) =1.17, 95% CI 1.06-1.30, P=0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis).

    CONCLUSIONS: Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  8. Fulltext KCNQ1 haplotypes associate with type 2 diabetes in Malaysian Chinese Subjects
    Saif-Ali R, Ismail IS, Al-Hamodi Z, Al-Mekhlafi HM, Siang LC, Alabsi AM, et al.
    Int J Mol Sci, 2011;12(9):5705-18.
    PMID: 22016621 DOI: 10.3390/ijms12095705
    The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) and haplotypes of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with type 2 diabetes (T2D) in Malaysian Chinese subjects. The KCNQ1 SNPs rs2237892, rs2283228 and rs2237895 were genotyped in 300 T2D patients and 230 control subjects without diabetes and metabolic syndrome. Two logistic regression models of analysis were applied, the first adjusted for age and gender while the second adjusted for age, gender and body mass index. The additive genetic analysis showed that adjusting for body mass index (BMI) even strengthened association of rs2237892, rs2283228 and rs2237895 with T2D (OR = 2.0, P = 5.1 × 10(-5); OR = 1.9, P = 5.2 × 10(-5); OR = 1.9, P = 7.8 × 10(-5), respectively). The haplotype TCA containing the allele of rs2237892 (T), rs2283228 (C) and rs2237895 (A) was highly protective against T2D (Second model; OR = 0.17, P = 3.7 × 10(-11)). The KCNQ1 rs2237892 (TT), and the protective haplotype (TCA) were associated with higher beta-cell function (HOMA-B) in normal subjects (P = 0.0002; 0.014, respectively). This study found that KCNQ1 SNPs was associated with T2D susceptibility in Malaysian Chinese subjects. In addition, certain KCNQ1 haplotypes were strongly associated with T2D.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  9. Polymorphic variant Ser128Arg of E-Selectin is associated with breast cancer risk and high grade tumors
    Naidu R, Har YC, Taib NA
    Onkologie, 2011;34(11):592-7.
    PMID: 22104155 DOI: 10.1159/000334060
    The present study aimed to evaluate the association between the E-Selectin Ser128Arg polymorphism and breast cancer risk and clinicopathological characteristics of the patients.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  10. Variation in human genetic polymorphisms, their association with Helicobacter pylori acquisition and gastric cancer in a multi-ethnic country
    Schmidt HM, Ha DM, Taylor EF, Kovach Z, Goh KL, Fock KM, et al.
    J Gastroenterol Hepatol, 2011 Dec;26(12):1725-32.
    PMID: 21649724 DOI: 10.1111/j.1440-1746.2011.06799.x
    BACKGROUND AND AIM: The contribution of human genetic polymorphisms to Helicobacter pylori infection and gastric cancer (GC) development remains unclear due to geographic variation in the association between specific host genetic polymorphisms and GC. In the current study we investigated the association between polymorphisms related to immune and cancer-related pathways and H. pylori infection among the major ethnicities, Chinese, Malay and Indian, resident in Singapore and Malaysia as well as the association between these polymorphisms and GC development in ethnic Chinese patients.

    METHODS: Thirty-four polymorphisms in 26 genes were typed by mass spectrometry in 422 patients undergoing endoscopy (162 Chinese, 113 Indian and 87 Malay controls and 60 Chinese GC cases). Patients were assessed for evidence of H. pylori infection. Odds ratios (OR) and confidence intervals (CI) were obtained using logistic regression models.

    RESULT: The prevalence of 16 polymorphisms varied significantly among the ethnicities. In the Chinese subgroup, nominally significant associations were shown between (i) EBBR2+1963G (rs1801200) and H. pylori infection (per-allele OR: 0.48, 95% CI 0.23, 0.98, P = 0.04), (ii) PTGS2-1195G (rs689466) and an increased risk of GC on adjusting for H. pylori status (OR: 1.53, 95% CI 0.99, 2.37, P = 0.05), and (iii) IL1B-1473C (rs1143623) and a decreased risk of GC (OR: 0.64, 95% CI 0.41, 0.99, P = 0.05). Borderline significant associations were seen between IL2-330G (rs2069762) (OR 1.45, 95% CI 0.95, 2.15, P = 0.06) and IL13-1111T (rs1800925) (OR 0.65, 95% CI 0.42, 1.01, P = 0.06) and H. pylori infection.

    CONCLUSION: These findings contribute to the understanding of the genetic variation between ethnicities, which may influence H. pylori susceptibility and the outcome of infection.

    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  11. Glyoxalase I Ala111Glu gene polymorphism: No association with breast cancer risk but correlated with absence of progesterone receptor
    Naidu R, Har YC, Taib NA
    Pathol. Int., 2010 Sep;60(9):614-20.
    PMID: 20712647 DOI: 10.1111/j.1440-1827.2010.02568.x
    The aim of the present study was to evaluate the association between the Glyoxalase I (GLOI) Ala111Glu polymorphism and breast cancer risk among the major Malaysian ethnic groups, the Malays, Chinese and Indians, as well as clinico-pathological characteristics of these patients. Genotyping of GLOI gene was performed on blood samples obtained from 387 patients and 252 normal healthy women who had no history of any malignancy using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of GLOI polymorphism were not significantly different between the patients and normal individuals among the Malays (P= 0.721, 0.402), Chinese (P= 0.208, 0.079) and Indians (P= 0.612, 0.349), respectively. The Malay, Chinese and Indian women who were Glu/Glu homozygotes (P= 0.419, 0.093, 0.367), Ala/Glu heterozygotes (P= 0.648, 0.182, 0.402) and carriers of Glu allele (P= 0.402, 0.079, 0.349), respectively, were not associated with breast cancer risk. The Glu allele genotype was significantly associated with absence of progesterone receptor (P= 0.036). Thus, the polymorphic variant of the GLOI gene might not be a useful genetic marker to identify Malaysian Malay, Chinese or Indian women who could be at greater risk of developing breast cancer.

    Study site: Universiti Malaya Medical Centre (UMMC)
    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  12. Mutation spectrum of dystrophin gene in malaysian patients with Duchenne/Becker muscular dystrophy
    Rani AQ, Sasongko TH, Sulong S, Bunyan D, Salmi AR, Zilfalil BA, et al.
    J. Neurogenet., 2013 Jun;27(1-2):11-5.
    PMID: 23438214 DOI: 10.3109/01677063.2012.762580
    We undertook the clinical feature examination and dystrophin analysis using multiplex ligation-dependent probe amplification (MLPA) and direct DNA sequencing of selected exons in a cohort of 35 Malaysian Duchenne/Becker muscular dystrophy (DMD/BMD) patients. We found 27 patients with deletions of one or more exons, 2 patients with one exon duplication, 2 patients with nucleotide deletion, and 4 patients with nonsense mutations (including 1 patient with two nonsense mutations in the same exon). Although most cases showed compliance to the reading frame rule, we found two unrelated DMD patients with an in-frame deletion of the gene. Two novel mutations have been detected in the Dystrophin gene and our results were compatible with other studies where the majority of the mutations (62.8%) are located in the distal hotspot. However, the frequency of the mutations in our patient varied as compared with those found in other populations.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  13. Human leucocyte antigen determinants of susceptibility to Barrett's oesophagus in Asians--a preliminary study
    Rajendra S, Ackroyd R, Murad S, Mohan C, Ho JJ, Goh KL, et al.
    Aliment Pharmacol Ther, 2005 Jun 1;21(11):1377-83.
    PMID: 15932368
    Characteristic immune profiles have been demonstrated in gastro-oesophageal reflux disease. However, the genetic basis of gastro-oesophageal reflux disease remains unclear.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  14. CYP1A1 MspI Polymorphism and Cervical Carcinoma Risk in the Multi-Ethnic Population of Malaysia: a Case-Control Study
    Tan YH, Sidik SM, Syed Husain SN, Lye MS, Chong PP
    Asian Pac J Cancer Prev, 2016;17(1):57-64.
    PMID: 26838255
    BACKGROUND: Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism.

    MATERIALS AND METHODS: A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR.

    RESULTS: We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia.

    CONCLUSIONS: Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.

    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  15. Why is acute leukemia more common in males? A possible sex-determined risk linked to the ABO blood group genes
    Jackson N, Menon BS, Zarina W, Zawawi N, Naing NN
    Ann Hematol, 1999 May;78(5):233-6.
    PMID: 10391104
    Acute leukemia is more common in males at almost every age, and this fact remains unexplained. A study was carried out in northeast peninsular Malaysia, where the population is predominantly Malay, to examine whether there was a difference in ABO blood group distribution between males and females with acute leukemia (AL). The ABO blood groups of 109 male and 79 female patients with AL (98 ALL, 90 AML) were compared with those of 1019 controls. In the control population, 39.7% were group O. Among males with AL, 39.4% were group O, whereas among females with AL, the proportion was 24.1% (p=0.03). The same trend to a lower proportion of group O among females was seen if the group was divided into adult/pediatric or lymphoblastic/myeloblastic groups, though these differences were not statistically significant. If these findings can be confirmed, they suggest the presence of a "sex-responsive" gene near to the ABO gene locus on chromosome 9, which relatively protects group O women against AL, at least in our population. The existence of such a gene might also partly explain why acute leukemia, and possibly other childhood cancers, are more common in males.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  16. Fulltext De Novo Truncating Variants in the Last Exon of SEMA6B Cause Progressive Myoclonic Epilepsy
    Hamanaka K, Imagawa E, Koshimizu E, Miyatake S, Tohyama J, Yamagata T, et al.
    Am J Hum Genet, 2020 04 02;106(4):549-558.
    PMID: 32169168 DOI: 10.1016/j.ajhg.2020.02.011
    De novo variants (DNVs) cause many genetic diseases. When DNVs are examined in the whole coding regions of genes in next-generation sequencing analyses, pathogenic DNVs often cluster in a specific region. One such region is the last exon and the last 50 bp of the penultimate exon, where truncating DNVs cause escape from nonsense-mediated mRNA decay [NMD(-) region]. Such variants can have dominant-negative or gain-of-function effects. Here, we first developed a resource of rates of truncating DNVs in NMD(-) regions under the null model of DNVs. Utilizing this resource, we performed enrichment analysis of truncating DNVs in NMD(-) regions in 346 developmental and epileptic encephalopathy (DEE) trios. We observed statistically significant enrichment of truncating DNVs in semaphorin 6B (SEMA6B) (p value: 2.8 × 10-8; exome-wide threshold: 2.5 × 10-6). The initial analysis of the 346 individuals and additional screening of 1,406 and 4,293 independent individuals affected by DEE and developmental disorders collectively identified four truncating DNVs in the SEMA6B NMD(-) region in five individuals who came from unrelated families (p value: 1.9 × 10-13) and consistently showed progressive myoclonic epilepsy. RNA analysis of lymphoblastoid cells established from an affected individual showed that the mutant allele escaped NMD, indicating stable production of the truncated protein. Importantly, heterozygous truncating variants in the NMD(+) region of SEMA6B are observed in general populations, and SEMA6B is most likely loss-of-function tolerant. Zebrafish expressing truncating variants in the NMD(-) region of SEMA6B orthologs displayed defective development of brain neurons and enhanced pentylenetetrazole-induced seizure behavior. In summary, we show that truncating DNVs in the final exon of SEMA6B cause progressive myoclonic epilepsy.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  17. Genetic abnormalities in a large cohort of Coffin-Siris syndrome patients
    Sekiguchi F, Tsurusaki Y, Okamoto N, Teik KW, Mizuno S, Suzumura H, et al.
    J Hum Genet, 2019 Dec;64(12):1173-1186.
    PMID: 31530938 DOI: 10.1038/s10038-019-0667-4
    Coffin-Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  18. Fulltext Distribution of the Duffy genotypes in Malaysian Borneo and its relation to Plasmodium knowlesi malaria susceptibility
    de Silva JR, Amir A, Lau YL, Ooi CH, Fong MY
    PLoS One, 2019;14(9):e0222681.
    PMID: 31536563 DOI: 10.1371/journal.pone.0222681
    The Duffy blood group plays a key role in Plasmodium knowlesi and Plasmodium vivax invasion into human erythrocytes. The geographical distribution of the Duffy alleles differs between regions with the FY*A allele having high frequencies in many Asian populations, the FY*B allele is found predominately in European populations and the FY*Bes allele found predominantly in African regions. A previous study in Peninsular Malaysia indicated high homogeneity of the dominant FY*A/FY*A genotype. However, the distribution of the Duffy genotypes in Malaysian Borneo is currently unknown. In the present study, the distribution of Duffy blood group genotypes and allelic frequencies among P. knowlesi infected patients as well as healthy individuals in Malaysian Borneo were determined. A total of 79 P. knowlesi patient blood samples and 76 healthy donor samples were genotyped using allele specific polymerase chain reaction (ASP-PCR). Subsequently a P. knowlesi invasion assay was carried out on FY*AB/ FY*A and FY*A/ FY*A Duffy genotype blood to investigate if either genotype conferred increased susceptibility to P. knowlesi invasion. Our results show almost equal distribution between the homozygous FY*A/FY*A and heterozygous FY*A/FY*B genotypes. This is in stark contrast to the Duffy distribution in Peninsular Malaysia and the surrounding Southeast Asian region which is dominantly FY*A/FY*A. The mean percent invasion of FY*A/FY*A and FY*A/FY*B blood was not significantly different indicating that neither blood group confers increased susceptibility to P. knowlesi invasion.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  19. The endothelial nitric oxide synthase gene G894T, glutathione S-transferase (GSTM1 and GSTT1) polymorphisms as a risk factor in the patient with nephrolithiasis
    Mehdi WA, Mehde AA, Yusof F, Raus RA, Resen AK, Ghazali H
    Int J Biol Macromol, 2019 Nov 01;140:719-726.
    PMID: 31445152 DOI: 10.1016/j.ijbiomac.2019.08.184
    BACKGROUND: The genetic features indicate a crucial role in nephrolithiasis. The present study was aimed to investigate the role of Glutathione-S-transferase Mu (GSTM1), Glutathione-S- transferase Theta (GSTT1) and endothelial nitric oxide synthase (eNOs) gene polymorphism in nephrolithiasis.

    METHODS: We involved a case-control study in which 480 individuals were divided into 240 healthy control and 240 patients with nephrolithiasis. For each patient and control, we measured biochemical criteria, levels of glutathione S-transferase, eNOs, GSTM1, GSTT1genes and eNOS genes polymorphism by PCR-RFLP.

    RESULTS: GSTM1 and GSTT1 null genotypes are not a risk features for nephrolithiasis. The eNOS frequency GG, GT, and TT genotypes by using Ban II enzyme as restriction enzyme were found to be (48.33, 36.67, and 15.00) %. The eNOS frequency TT, GT, and GG genotypes by using the Ban II enzyme as restriction enzyme were found to be 15.84, 25.83, and 58.33%, respectively. The result showed an increase in serum eNOs levels were in the patient's group comparing to control.

    CONCLUSIONS: This work is the first in the literature to study the relation between eNOs genes polymorphisms and nephrolithiasis. The results conclude that TT genotypes in the eNOs genes are associated with an increase the oxidative stress in patients.

    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  20. Lack of correlation between X-ray repair cross-complementing group 1 gene polymorphisms and the susceptibility to colorectal cancer in a Malaysian cohort
    Lau TP, Lian LH, Cheah PL, Looi LM, Roslani AC, Goh KL, et al.
    Eur J Cancer Prev, 2017 11;26(6):506-510.
    PMID: 28059856 DOI: 10.1097/CEJ.0000000000000336
    X-ray repair cross-complementing group 1 (XRCC1) is one of the key components in the base excision repair pathway that repairs erroneous DNA lesions and removes nonbulky base adducts for the maintenance of genome integrity. Studies have revealed that differences in individual DNA repair capacity can impact the interindividual variation in cancer susceptibility, tumour aggressiveness and treatment response. The relationship between XRCC1 and sporadic colorectal cancer (CRC) susceptibility, which is hitherto inconclusive, has been explored in many association studies of different populations. In view of the conflicting findings generated, we aimed to investigate the association between XRCC1 and genetic predisposition to CRC among Malaysians. The present case-control association study was conducted on 130 CRC patients and 212 age-matched healthy controls. The genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln single nucleotide polymorphisms was performed with allele-specific real-time PCR approach. This was followed by basic statistical analysis on the single nucleotide polymorphisms and haplotype data obtained. No significant difference in the allele and genotype frequencies was observed between CRC patients and healthy controls (P>0.05). There was also no association observed between XRCC1 haplotypes and CRC (P>0.05). In conclusion, a positive association between XRCC1 gene polymorphisms and CRC risk was not established in our Malaysian population.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
Related Terms
Filters
Contact Us

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

External Links