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The –514 CT Hepatic Lipase Promoter Region Polymorphism and Plasma Lipids: A Meta-Analysis

Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. C. M. van Duijn, Department of Epidemiology and Biostatistics, Erasmus Medical Center, Postbus 1738, 3000 DR Rotterdam, The Netherlands. E-mail: c.vanduijn{at}erasmusmc.nl.

Investigations of the –514 CT single nucleotide polymorphism (SNP) in the hepatic lipase (HL) gene promoter region (LIPC) have yielded contradictory results regarding its association with changes in plasma lipids. The current study is a meta-analysis of 25 publications on this SNP, comprising over 24,000 individuals, and its relationship with total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL), triglycerides, and HL activity. Significant decreases were observed in HL activity for both the CT and TT genotypes compared with the CC genotype [weighted mean difference (WMD), –5.83 mmol/liter·h (95% confidence interval, –8.48, –3.17) and –11.05 mmol/liter·h (95% confidence interval, –14.74, –7.36), respectively]. Moreover, significant increases in HDL were found; the CT to CC comparison showed an increase in WMD of 0.04 mmol/liter (95% confidence interval, 0.02, 0.05) mmol/liter, and the increase in the TT vs. CC difference was WMD of 0.09 mmol/liter (95% confidence interval, 0.07, 0.12). These changes appear to be stepwise, implying an allele dosage effect. All P values for these associations were less than 0.001. This meta-analysis demonstrates the importance of the –514CT SNP in determining HL activity and plasma HDL concentration and helps quantify the role that hepatic lipase plays in the metabolism of HDL.

Abbreviations: CAD, Coronary artery disease; HDL, high-density lipoprotein cholesterol; HL, hepatic lipase; HWE, Hardy-Weinberg equilibrium; LDL, low-density lipoprotein cholesterol; SNP, single nucleotide polymorphism; TC, total cholesterol; WMD, weighted mean difference.

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