METHODS: A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).
RESULTS: Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes.
CONCLUSION: Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.
METHODS: Demographic, clinical and genotype data were determined for 1122 women (267 cases and 855 controls) recruited from the University of Malaya Medical Centre in the Klang Valley, Kuala Lumpur. Relevant articles were identified from Pubmed, Embase, MEDLINE, and Web of Science. Extraction of data was carried out and summary estimates of the association between rs780094 and GDM were examined.
RESULTS: The frequency of risk allele C was significantly higher in the cases than controls (OR 1.34, 95% CI 1.09-1.66, P = 0.006). The C allele was also associated with increased level of random 2-hour fasting plasma glucose and pregravid body mass index. Meta-analysis further confirmed the association of the GCKR rs780094 with GDM (OR 1.32, 95% CI 1.14-1.52, P = 0.0001).
CONCLUSION: This study strongly suggests that GCKR rs780094-C is associated with increased risk of GDM.
METHODS: The 114 healthy volunteers were recruited for this study, and their DNA was extracted. Primer pair was designed using Primer 3 Software version 0.4.0 and validated against the BLAST database. The primer specificity, functionality and annealing temperature were tested using uniplex PCR methods that were later combined into a single multiplex PCR. Restriction Fragment Length Polymorphism (RFLP) was performed in three separate tubes followed by agarose gel electrophoresis. PCR product residual was purified and sent for DNA sequencing.
RESULTS: The allele frequencies for MTHFR 677 C > T were 0.89 (C allele) and 0.11 (T allele); for eNOS +894 G > T, the allele frequencies were 0.58 (G allele) and 0.43 (T allele); and for eNOS -786 T > C, the allele frequencies were 0.87 (T allele) and 0.13 (C allele).
CONCLUSIONS: Our PCR-RFLP method is a simple, cost-effective and time-saving method. It can be used to successfully genotype subjects for the MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C variants simultaneously with 100% concordance from DNA sequencing data. This method can be routinely used for rapid investigation of the MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C variants.
AIM: This study aims to investigate the genetic polymorphisms of CYP3A5 among the Orang Asli in Peninsular Malaysia using a next generation sequencing platform.
METHODS: Genomic DNAs were extracted from blood samples of the three main Orang Asli tribes and whole-genome sequencing was performed.
RESULTS: A total of 61 single nucleotide polymorphisms were identified and all the SNPs were located in introns except rs15524, which is in the 3'UTR, and 11 of these polymorphisms were novel. Two allelic variants and three genotypes were identified in the Orang Asli. The major allelic variant was the non-functional CYP3A5*3 (66.4%). The percentages of Orang Asli with CYP3A5*3/*3 (47.2%) and CYP3A5*1/*3 (38.1%) genotypes are more than twice the percentage of Orang Asli with CYP3A5*1/*1 (14.8%) genotype. Almost half of the Orang Asli harboured CYP3A5 non-expressor genotype (CYP3A5*3/*3).
CONCLUSIONS: The predominance of the CYP3A5 non-expressor genotype among the Orang Asli was unravelled and the findings in this study may serve as a guide for the optimisation of pharmacotherapy for the Orang Asli community.
METHODS: This study included 1740 males (1146 Chinese, 327 Malays and 267 Asian Indians) and 1950 females (1329 Chinese, 360 Malays and 261 Asian Indians) with complete data on anthropometric indices, fasting lipids, smoking status, alcohol consumption, exercise frequency and genotype at the APOE locus.
RESULTS: Malays and Asian Indians were more obese compared with the Chinese. Smoking was uncommon in all females but Malay males had significantly higher prevalence of smokers. Malays had the highest LDL-C whilst Indians had the lowest HDL-C, The epsilon 3 allele was the most frequent allele in all three ethnic groups. Malays had the highest frequency of epsilon 4 (0.180 and 0.152) compared with Chinese (0.085 and 0.087) and Indians (0.108 and 0.075) in males and females, respectively. The epsilon 2 allele was the least common in Asian Indians. Total cholesterol (TC) and LDL-C was highest in epsilon 4 carriers and lowest in epsilon 2 carriers. The reverse was seen in HDL-C with the highest levels seen in epsilon 2 subjects. The association between ethnic group and HDL-C differed according to APOE genotype and gender. Asian Indians had the lowest HDL-C for each APOE genotype except in Asian Indian males with epsilon 2, where HDL-C concentrations were intermediate between Chinese and Malays.
CONCLUSION: Ethnic differences in lipid profile could be explained in part by the higher prevalence of epsilon 4 in the Malays. Ethnicity may influence the association between APOE genotypes and HDL-C. APOE genotype showed no correlation with HDL-C in Malay males whereas the association in Asian Indians was particularly marked. Further studies of interactions between genes and environmental factors will contribute to the understanding of differences of coronary risk amongst ethnic groups.