Strong linkage disequilibrium and association of -1131T>C and c.553G>T polymorphisms of the apolipoprotein A5 gene with hypertriglyceridemia in a Japanese population.
BACKGROUND
The apolipoprotein A5 gene (ApoA5) plays an important role in modulating triglyceride metabolism. Polymorphisms of ApoA5, including -1131T>C and c.553G>T (G185C), have been reported to correlate with hypertriglyceridemia (HTG). In the present study the relationships of 5 single nucleotide polymorphisms, including the -1131T>C, c.56C>G, IVS3+476G>A, c.553G>T, and c.1259T>C polymorphisms of ApoA5, with HTG were investigated.


RESULTS
The study group comprised 95 Japanese patients with HTG and 119 unrelated normolipidemic subjects. Frequencies of the C allele of -1131T>C (0.511) and the T allele of c.553G>T (0.205) in the hypertriglyceridemic patients were significantly higher than in the normolipidemic subjects (0.315 and 0.105, respectively). The c.56C>G (S19W) polymorphism was not observed, and the other 4 polymorphic sites were in strong linkage disequilibrium. Five of the 8 detected haplotypes with the C allele of -1131T>C correlated with HTG. Promoter activities of ApoA5, including that with the -1131T>C polymorphism, were estimated using a luciferase assay. Analysis of ApoA5 promoters showed that the -1131T>C polymorphism alone had no effect. Comparison of expression of mutant G185C and wild-type ApoA5-green fluorescent protein (GFP) in HepG2 cells showed that ApoA5-GFP was abundant in punctate endosome-like structures, and ApoA5 (G185C)-GFP expression resembled that of the wild type.


CONCLUSIONS
The -1131T>C and c.553G>T (G185C) polymorphisms correlated with HTG in this Japanese population, but neither polymorphism directly affected ApoA5 expression.
Matsunaga
Akira
A
Department of Cardiology, Fukuoka University School of Medicine, Johnan-ku, Fukuoka, Japan. matsunag@cis.fukuoka-u.ac.jp
Arishima
Hiroaki
H
Niimura
Hideya
H
Zhang
Bo
B
Uehara
Yoshinari
Y
Ohwaki
Kazuo
K
Morita
Mie
M
Hayashida
Kazue
K
Saku
Keijiro
K
D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D003596:Cytosine; D005260:Female; D005787:Gene Frequency; D006147:Guanine; D006239:Haplotypes; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013941:Thymine; D014018:Tissue Distribution
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D006147:Guanine; D003596:Cytosine; D013941:Thymine