A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity

Abstract

Hepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of plasma lipoproteins, especiallyHDLs. Association of the polymorphisms in the promoter region of the LIPC gene to post-heparin plasma HL activity and the plasma HDL-C concentration has been investigated thoroughly, but to date little is known about this in the Chinese. In the present study, we analyzed the polymorphisms in the promoter region of LIPC gene in Chinese patients with coronary artery disease (CAD) using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. As the result, a novel single nucleotide polymorphism ؊ 586T-to-C was identified and no linkage of this variant with other polymorphisms in the promoter was found. Compared with the nonsymptomatic control subjects, excess of carriers of the ؊ 586T/C substitution were detected in the CAD patients (43% vs. 31%, 2 ‫؍‬ 4.597, degree of freedom ‫؍‬ 2, P ‫؍‬ 0.032).The -586C allele carriers in the CAD patients had a significantly higher HDL-C level than the noncarriers (1.13 ؎ 0.24 mmol/l vs. 0.91 ؎ 0.14 mmol/l, P Ͻ 0.05). To test the functionality of this substitution, luciferase-reporter assays was performed in HepG2 cells. Promoter activity of the ؊ 586C construct was decreased 2-fold than the ؊ 586T construct.Our studies suggest that a T-to-C substitution at ؊ 586 of the LIPC promoter is associated with a lowered HL activity and that this variation may contribute to the increased plasma HDL-C concentration in the Chinese.

Polymorphisms in the hepatic lipase gene affect plasma HDL-cholesterol levels in a Turkish population

“…The -586C>T SNP was associated with increased HDL-C levels. Luciferase reporter assays suggested that the minor T allele decreased promoter activity ( 54 ). The two other variants, -2T>C ( 55 ) and R276L ( 56 ), had signifi cantly higher allelic frequencies in coronary heart disease patients than control subjects.…”

“…This variant was not associated with lipid parameters in Turks. Recently, three novel SNPs with high allelic frequencies (21-25%) were reported in a Han Chinese population (54)(55)(56). The -586C>T SNP was associated with increased HDL-C levels.…”

Association between DNA variant sites in the apolipoprotein A5 gene and coronary heart disease in Chinese

“…Four hundred eighty-three unrelated CHD patients were selected between 2000 and 2004 from the West China Hospital, Sichuan University, for the study by coronary angiography, using the Judkins technique [14]. Individuals having any major coronary artery branch (left anterior descending artery, left circumflex artery, right coronary artery) with at least 1 stenosis of N60% were qualified as CHD patients.…”

The G‐250A substitution in the promoter region of the hepatic lipase gene is associated with the conversion from impaired glucose tolerance to type 2 diabetes: the STOP‐NIDDM trial

“…HL activity is influenced by gender, sex-steroid hormones, intra-abdominal fat (IAF) and variants in the hepatic lipase gene (LIPC) [5,7,[10][11][12].…”