Genetic contribution to variation in atherothrombotic phenotypes in the Asian Indian population

Veena S. Rao; Natesha B. Khadrinarasimhaih; Saikat Kanjilal; Manjari Mukerjee; Vijay V. Kakkar

doi:10.1160/TH08-01-0018

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(02): 379-388
DOI: 10.1160/TH08-01-0018

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Genetic contribution to variation in atherothrombotic phenotypes in the Asian Indian population

The Indian Atherosclerosis Research Study

Authors

Veena S. Rao

¹Tata Proteomics and Coagulation Unit, Thrombosis Research Institute, Bangalore, India
Natesha B. Khadrinarasimhaih

¹Tata Proteomics and Coagulation Unit, Thrombosis Research Institute, Bangalore, India
Saikat Kanjilal

²Clinical Research Unit, Thrombosis Research Institute, Bangalore, India
Manjari Mukerjee

¹Tata Proteomics and Coagulation Unit, Thrombosis Research Institute, Bangalore, India
Vijay V. Kakkar

³Narayana Hrudayalaya Hospital, Bangalore, India

⁴Thrombosis Research Institute, Emmanuel Kaye Building, Chelsea, London, UK

Abstract

Summary

Coronary artery disease (CAD) is a multifactorial disease, and family history is the best available tool to assess gene-environment interaction. This study addressed the heritability of quantitative traits, namely lipid, coagulation/fibrinolysis and pro-inflammatory markers in the ongoing family-based Indian Atherosclerosis Research Study and assessed the effect of the type/lineage of CAD family history on inheritance patterns in the highrisk Indian population. A total of 518 families comprising 2,305 individuals were recruited in phase I of the IARS; of these, 1,195 individuals from 220 families were included in the heritability analysis. With the exception of leptin, all phenotypes exhibited significant age- and sex-adjusted heritability (p<0.0001). Amongst all the phenotypes analysed after adjustment for confounding factors, the significantly higher heritability estimates of triglycerides (0.53, p<0.0001), lipoprotein (a) (0.83, p<0.0001) and interleukin-6 (0.46, p<0.0001) with low spouse pair correlations identifies them as possible CAD risk factors. Families with parental history of CAD had onset of CAD symptoms at much younger ages with significantly higher heritability of proinflammatory markers, whereas in families with sibling history of CAD, more risk factors were present at significantly higher levels. Triglycerides, lipoprotein (a) and interleukin-6 appear to be promising atherothrombotic candidate phenotypes in this population. Genes controlling these phenotypes are possible candidate genes linked with CAD. An informed understanding and incorporation of ‘family history’ as a screening tool may help in the prevention and pre-emption of CAD.

Keywords

Inflammation - SOLAR - atherosclerosis

Full Text

References

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