Summary
Inflammation plays a major role in coronary artery disease (CAD). We investigated
the polymorphisms in the interleukin 6 (IL6) gene and their effect on the expression of acute-phase proteins in premature CAD
in Asian Indian families. One hundred and ninety affected sibling pairs (ASPs) were
genotyped for three tag single nucleotide polymorphisms (SNPs) in the IL6 gene for linkage analysis. We observed suggestive logarithm of odds (LOD) score for
one SNP (rs2066992) in a subset of 62 ASPs with the age at onset less than 45 years
(LOD score = 1.114, p = 0.011 in linkage analysis; pi = 0.55, p = 0.008 in identity
by descent; LOD score = 1.06, p = 0.014 in quantitative trait locus for plasma levels
of high sensitivity C-reactive protein, hsCRP). This was followed by sequencing of
the promoter region and haplotype analysis in 46 probands and 40 controls. Five out
of the eight previously reported promoter SNPs were found to be polymorphic (rs1800797,
rs1800796, rs7802307, rs7802308, rs1800795). Two novel sequence variants were also
found. One promoter haplotype (GGAAG) was detected with an odds ratio (OR) of 3.676
(p = 0.0017, 95% confidence interval [CI]: 1.68 – 8.045) and population attributable
risk of 21.1% (95%CI: 9.2%-31.5%). The plasma levels of both hsCRP and fibrinogen
exhibited significant association with these promoter SNP genotypes (p < 0.001). In
conclusion, IL6 gene polymorphisms appear to be important genetic factors in premature CAD, and in
the regulation of key atherogenic markers in Asian Indian families.
Keywords
Asian Indians - CAD - IL6 - CRP - fibrinogen