The S447X variant of lipoprotein lipase gene is inversely associated with severity of coronary artery disease

Abstract

Hyperlipidemia is a major risk factor for coronary artery disease (CAD). Lipoprotein lipase (LPL) is an important enzyme in lipoprotein metabolism. S447X polymorphism of the LPL gene has been implicated in the pathogenesis of CAD. Carriers of X447 allele were reported to have lower triglyceride and higher high-density lipoprotein cholesterol levels as well as a reduced risk of CAD. We hypothesized that S447X gene polymorphism might have a protective effect for CAD. A total of 178 subjects (mean age 42.97 ± 6.5 years) who underwent coronary angiography for clinical indications were included in the study. The patients had been referred for evaluation of chest pain and/or abnormal stress tests, and were selected consecutively. Gensini scores were used to assess the severity of CAD; 97 patients were diagnosed with angiographically proven CAD, and 81 subjects did not display significant CAD (≥ 70%) angiographically. Genotyping of LPL S447X polymorphism was performed by real-time polymerase chain reaction amplification and fluorescent probe melting point analysis on the light cycler. The minor allele frequencies of LPL 447X allele were 11.1% and 6.2% among subjects without CAD compared with CAD subjects (P = 0.081) and 447X allele had favorable effects on lipid levels among CAD patients; 447X homozygotes and heterozygotes displayed lower total cholesterol (171 ± 37 vs 208 ± 48 mg/dl, P = 0.02), lower triglycerides (121 ± 72 vs 184 ± 86 mg/dl, P = 0.02), lower low-density lipoprotein cholesterol (102 ± 27 vs 129 ± 39 mg/dl, P = 0.03). Gensini scores were significantly lower among the heterozygotes and homozygotes of LPL 447X allele than in the LPL S447 homozygotes (15 ± 23 vs 25 ± 30, P = 0.048). S447X polymorphism of LPL gene may have a protective role for the severity of CAD. The beneficial effects of S447X polymorphism of the LPL gene may be through its favorable effects on lipid levels.

A novel lipoprotein lipase gene missense mutation in Chinese patients with severe hypertriglyceridemia and pancreatitis

“…In a previous study, LPL S447X mutation was shown to have a naturally occurring gain-function [18]. This LPL mutation S447X is the only mutation that has a protective effect against the development of HTG and coronary heart disease by decreasing plasma TG levels in the clinic and increasing HDL production [19]. Thus, gene therapy using the S447X variant has shown therapeutic promise in the study of LPL deficiency [20].…”

Study of common variants of the apolipoprotein E and lipoprotein lipase genes in patients with coronary heart disease and variable body mass index

“…36 Agirbasli M et al reported that the S447X variant of the LPL gene is inversely associated with severity of CHD and lower TG and HDL-C levels. 37 Also in a recent study, the LPL gene polymorphism was shown to be associated with the consumption of alcohol and unsaturated fat and to modulate serum HDL-C levels. Specifically, the X allele was positively associated with HDL-C concentrations (p<0.001).…”

Variants of D9N, G188A, N291S, and 93 T/G Genes in patients with Coronary Artery Diseases

“…Several genetic LPL mutations and metabolic disturbances that alter the lipid and lipoprotein metabolism have been reported as CAD risk factors. (20).…”