title: An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients.
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.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA, USA. clive.pullinger@ucsf.edu
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
authors.forename: Irina
authors.initials: I
authors.lastname: Movsesyan
authors.forename: Vincent
authors.initials: V
authors.lastname: Durlach
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Nakajima
authors.forename: Annie
authors.initials: A
authors.lastname: Poon
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hattori
authors.forename: Lauri L
authors.initials: LL
authors.lastname: Green
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Havel
authors.forename: Philip H
authors.initials: PH
authors.lastname: Frost
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Malloy
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
mesh_terms: D000328:Adult; D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D001213:Asian / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002681:China / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A