Key result
The C allele of the ApoA5 -1131T>C polymorphism was significantly more frequent in Japanese patients with hypertriglyceridemia (51.1%) compared to normolipidemic controls (31.5%, p<0.01).
Why the study?
Do ApoA5 gene polymorphisms (-1131T>C and c.553G>T) increase the risk of hypertriglyceridemia in a Japanese population?
Case-Control (n=214)
No
Do ApoA5 gene polymorphisms (-1131T>C and c.553G>T) increase the risk of hypertriglyceridemia in a Japanese population?
Absolute Event Rate: 51.1% vs 31.5%
p-value: p=<0.01
The -1131T>C and c.553G>T polymorphisms of the ApoA5 gene are significantly associated with hypertriglyceridemia in the Japanese population, though they do not appear to directly alter ApoA5 expression in vitro.
May support genetic risk stratification in Japanese hypertriglyceridemia; leaves open causality and clinical utility pending prospective validation.
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. METHODS AND 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.
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Matsunaga et al. (2007) conducted a case-control in Hypertriglyceridemia (n=214). ApoA5 -1131T>C and c.553G>T polymorphisms vs. Normolipidemic controls was evaluated on Frequency of the C allele of the -1131T>C polymorphism (p=<0.01). The C allele of the ApoA5 -1131T>C polymorphism was significantly more frequent in Japanese patients with hypertriglyceridemia (51.1%) compared to normolipidemic controls (31.5%, p<0.01).
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