Abstract
Apolipoprotein A-V (apoA-V) is an important regulator of plasma levels of triglyceride (TG) in mice. In humans, APOA5 genetic variation is associated with TG in several populations. In this study, we determined the effects of the p.185Gly>Cys (c.553G>T; rs2075291) polymorphism on plasma TG levels in subjects of Chinese ancestry living in the United States and in a group of non-Chinese Asian ancestry. The frequency of the less common cysteine allele was 4-fold higher (15.1% vs. 3.7%) in Chinese high-TG subjects compared with a low-TG group (Chi-square = 20.2; P < 0.0001), corresponding with a 4.45 times higher risk of hypertriglyceridemia (95% confidence interval, 2.18-9.07; P < 0.001). These results were replicated in the non-Chinese Asians. Heterozygosity was associated, in the high-TG group, with a doubling of TG (P < 0.001), mainly VLDL TG (P = 0.014). All eleven TT homozygotes had severe hypertriglyceridemia, with mean TG of 2,292 +/- 447 mg/dl. Compared with controls, carriers of the T allele had lower postheparin lipoprotein lipase activity but not hepatic lipase activity. In Asian populations, this common polymorphism can lead to profound adverse effects on lipoprotein profiles, with homozygosity accounting for a significant number of cases of severe hypertriglyceridemia. This specific apoA-V variant has a pronounced effect on TG metabolism, the mechanism of which remains to be elucidated.
Highlights
Apolipoprotein A-V is an important regulator of plasma levels of triglyceride (TG) in mice
We have shown in three dyslipidemic populations that the rare allele of the single nucleotide polymorphism (SNP) rs662799 (21131T.C) in the promoter of APOA5 is associated with elevated TG and VLDL cholesterol (VLDL-C) and with lower levels of HDL [15]
P values were calculated by unpaired Students t-test, except for the female value, which was by Chi-square test
Summary
Apolipoprotein A-V (apoA-V) is an important regulator of plasma levels of triglyceride (TG) in mice. The frequency of the less common cysteine allele was 4-fold higher (15.1% vs 3.7%) in Chinese high-TG subjects compared with a low-TG group (Chi-square 5 20.2; P , 0.0001), corresponding with a 4.45 times higher risk of hypertriglyceridemia (95% confidence interval, 2.18–9.07; P , 0.001) These results were replicated in the non-Chinese Asians. In Asian populations, this common polymorphism can lead to profound adverse effects on lipoprotein profiles, with homozygosity accounting for a significant number of cases of severe hypertriglyceridemia. This specific apoA-V variant has a pronounced effect on TG metabolism, the mechanism of which remains to be elucidated.—Pullinger, C. It is a significant element in the metabolic syndrome, a constellation of clinical features linking insulin resistance, hyperlipidemia, low HDL cholesterol (HDL-C), diabetes, obesity, and hypertension with CAD
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