A two-step genetic study on quantitative precursors of coronary artery disease in a homogeneous Indian population: Case–control association discovery and validation by transmission-disequilibrium test.
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Date
2011-12
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Abstract
In spite of its strong familiality, gene identification for coronary artery disease (CAD) has not yielded a consistent
picture. One major reason for this is that families or cases and controls were not recruited from a homogeneous
population. We, therefore, attempted to map genes underlying 10 quantitative traits (QTs) that are known precursors
of CAD in a homogeneous population (Marwari) of India. The QTs are apolipoprotein B (ApoB), C-reactive protein
(CRP), fibrinogen (FBG), homocysteine (HCY), lipoprotein (a) (LPA), cholesterol – total (CHOL-T), cholesterol –
HDL (CHOL-H), cholesterol – LDL (CHOL-L), cholesterol – VLDL (CHOL-V) and triglyceride (TG). We assayed
209 SNPs in 31 genes among members of Marwari families. After log-transformation and covariate-adjustment of
the QTs, a two-step analysis was performed. In Step-1, data on unrelated individuals were analysed for association
with the SNPs. In Step-2, for validation of Step-1 results, a quantitative transmission-disequilibrium test on parent–
offspring data was performed for each SNP found to be significantly associated with a QT in Step-1 on an
independent sample set drawn from the same population. Statistically significant results found for the various QTs
and SNPs were: rs3774933, rs230528, rs230521, rs1005819 and rs1609798 (intronic, NFKB1) with APOB; rs5361
(Missense, R>S, SELE) and rs4648004 (Intronic, NFKB1) with FBG; rs4220 (Missense, K>R, FGB) with HCY; and
rs3025035 (Intronic, VEGFA) with CHOL-H. SNPs in SELE, VEGFA, FGB and NFKB1 genes impact significantly
on levels of quantitative precursors of CAD in Marwaris.
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Keywords
Candidate gene, coronary artery disease, genomic polymorphism, quantitative trait
Citation
Mallik Sanjukta, Majumder Partha P. A two-step genetic study on quantitative precursors of coronary artery disease in a homogeneous Indian population: Case–control association discovery and validation by transmission-disequilibrium test. Journal of Biosciences. 2011 Dec; 36 (5): 857-868.