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 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.
Isaacs
Aaron
A
Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
Sayed-Tabatabaei
Fakhredin A
FA
Njajou
Omer T
OT
Witteman
Jacqueline C M
JC
van Duijn
Cornelia M
CM
D003596:Cytosine; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013941:Thymine
C504173:LIPC protein, human; D003596:Cytosine; D008049:Lipase; D013941:Thymine