Polymorphisms in the IL6 gene in Asian Indian families with premature coronary artery disease – The Indian Atherosclerosis Research Study

Arindam Maitra; Jayashree Shanker; Debabrata Dash; Shibu John; Prathima R. Sannappa; Veena S. Rao; Jayakumar K. Ramanna; Vijay V. Kakkar

doi:10.1160/TH07-11-0686

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(05): 944-950
DOI: 10.1160/TH07-11-0686

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Polymorphisms in the IL6 gene in Asian Indian families with premature coronary artery disease – The Indian Atherosclerosis Research Study

Arindam Maitra

¹Mary & Garry Weston Functional Genomics Unit, Thrombosis Research Institute, Bangalore, India

,

Jayashree Shanker

¹Mary & Garry Weston Functional Genomics Unit, Thrombosis Research Institute, Bangalore, India

,

Debabrata Dash

¹Mary & Garry Weston Functional Genomics Unit, Thrombosis Research Institute, Bangalore, India

,

Shibu John

²Elizabeth & Emmanuel Kaye Bioinformatics and Statistics Unit, Thrombosis Research Institute, Bangalore, India

,

Prathima R. Sannappa

¹Mary & Garry Weston Functional Genomics Unit, Thrombosis Research Institute, Bangalore, India

,

Veena S. Rao

³Tata Proteomics & Coagulation Unit, Thrombosis Research Institute, Bangalore, India

,

Jayakumar K. Ramanna

⁴Clinical Research Unit, Thrombosis Research Institute, Bangalore, India

,

Vijay V. Kakkar

⁵Emeritus Professor of University of London, London, UK

⁶Chairman, Thrombosis Research Institute, Bangalore, India

⁷Director, Thrombosis Research Institute, London, UK

› Author Affiliations

Abstract

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

Full Text

References

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