TY - JOUR
T1 - An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients
AU - Pullinger, Clive R.
AU - Aouizerat, Bradley E.
AU - Movsesyan, Irina
AU - Durlach, Vincent
AU - Sijbrands, Eric J.
AU - Nakajima, Katsuyuki
AU - Poon, Annie
AU - Dallinga-Thie, Geesje M.
AU - Hattori, Hiroaki
AU - Green, Lauri L.
AU - Kwok, Pui Yan
AU - Havel, Richard J.
AU - Frost, Philip H.
AU - Malloy, Mary J.
AU - Kane, John P.
PY - 2008/8
Y1 - 2008/8
N2 - 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 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. 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.
AB - 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 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. 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.
KW - Chinese Americans
KW - Haplotypes
KW - Heart disease
KW - High density lipoprotein
KW - Lipoprotein lipase
KW - Polymorphism
KW - Single nucleotide polymorphism
KW - Triglycerides
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U2 - 10.1194/jlr.P800011-JLR200
DO - 10.1194/jlr.P800011-JLR200
M3 - Article
C2 - 18441017
AN - SCOPUS:51449114710
SN - 0022-2275
VL - 49
SP - 1846
EP - 1854
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 8
ER -