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American Journal of Epidemiology Advance Access originally published online on October 15, 2008
American Journal of Epidemiology 2008 168(11):1233-1246; doi:10.1093/aje/kwn235
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Seven Lipoprotein Lipase Gene Polymorphisms, Lipid Fractions, and Coronary Disease: A HuGE Association Review and Meta-Analysis

Gurdeep S. Sagoo, Iain Tatt, Georgia Salanti, Adam S. Butterworth, Nadeem Sarwar, Merel van Maarle, J. Wouter Jukema, Björn Wiman, John J. P. Kastelein, Anna M. Bennet, Ulf de Faire, John Danesh and Julian P. T. Higgins

Correspondence to Dr. Julian P. T. Higgins, MRC Biostatistics Unit, Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 0SR, United Kingdom (e-mail: julian.higgins{at}mrc-bsu.cam.ac.uk).

Received for publication January 31, 2008. Accepted for publication July 14, 2008.

Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism and a major candidate gene for coronary heart disease (CHD). The authors assessed associations between 7 LPL polymorphisms and lipid fractions and CHD risk in population-based cohort, case-control, and cross-sectional studies published by January 2007. Meta-analyses of 22,734 CHD cases and 50,177 controls in 89 association studies focused on the relations of the T-93G (rs1800590), D9N (rs1801177), G188E, N291S (rs268), PvuII (rs285), HindIII (rs320), and S447X (rs328) polymorphisms to high density lipoprotein cholesterol, triglycerides, myocardial infarction, or coronary stenosis. Carriers of 9N or 291S had modestly adverse lipid profiles. Carriers of the less common allele of HindIII or of 447X had modestly advantageous profiles. The combined odds ratio for CHD among carriers was 1.33 (95% confidence interval (CI): 1.14, 1.56) for 9N, 1.07 (95% CI: 0.96, 1.20) for 291S, 0.89 (95% CI: 0.81, 0.98) for the less common HindIII allele, and 0.84 (95% CI: 0.75, 0.94) for 447X. For T-93G (odds ratio (OR) = 1.22, 95% CI: 0.98, 1.52) and PvuII (OR = 0.96, 95% CI: 0.89, 1.04), there were null associations with lipid levels or CHD risk; information on G188E was limited (OR = 2.80, 95% CI: 0.88, 8.87). The study of LPL genotypes confirms the existence of close interrelations between high density lipoprotein cholesterol and triglyceride pathways. The influence of these genotypes on CHD risk warrants further investigation.

cholesterol, HDL; coronary disease; epidemiology; genetics; lipoprotein lipase; meta-analysis; myocardial infarction; triglycerides

Abbreviations: CHD, coronary heart disease; CI, confidence interval; HDL, high density lipoprotein; LPL, lipoprotein lipase


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