The −514 C→T Hepatic Lipase Promoter Region Polymorphism and Plasma Lipids: A Meta-Analysis

Investigations of the −514 C→T 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...

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Published in:The journal of clinical endocrinology and metabolism 2004-08, Vol.89 (8), p.3858-3863
Main Authors: Isaacs, Aaron, Sayed-Tabatabaei, Fakhredin A., Njajou, Omer T., Witteman, Jacqueline C. M., van Duijn, Cornelia M.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cytosine
Endocrinopathies
Fundamental and applied biological sciences. Psychology
Genotype
Humans
Lipase - genetics
Medical sciences
Polymorphism, Single Nucleotide
Promoter Regions, Genetic - genetics
Thymine
Vertebrates: endocrinology
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Summary:Investigations of the −514 C→T 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 −514C→T SNP in determining HL activity and plasma HDL concentration and helps quantify the role that hepatic lipase plays in the metabolism of HDL.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2004-0188