Association of V227A PPARα polymorphism with altered serum biochemistry and alcohol drinking in Japanese men
Association of V227A PPARα polymorphism with altered serum biochemistry and alcohol drinking in Japanese men
复制标题
DOI：
10.1097/01.fpc.0000220565.90466.79
复制
发表时间：
2006-08-01
影响因子：
2.6
通讯作者：
Nakajima, Tamie
中科院分区：
文献类型：
--
作者：
Naito, Hisao;Yamanoshita, Osamu;Nakajima, Tamie
目的过氧化物酶体增殖物激活受体（Peroxisome proliferator-activated receptor，PPARa）在啮齿类动物酒精性肝病中起重要作用。本研究的双重目的是确定日本人群中PPAR α多态性的存在及其频率，然后评估任何等位基因对代谢参数和饮酒的影响。从这些受试者中，在应用排除标准后，进一步研究了655名男性。结果在欧洲和北美没有报道过的PPAR α-V227 A作为主要的多态性，发现的频率为0.05。在欧洲和北美人群中发现了PPARalpha-L162 V，但在日本人群中未发现，从而证实了PPARalpha等位基因频率的种族差异。A227等位基因与血清γ谷氨酰转肽酶浓度升高相关。在非饮酒者中，总胆固醇（TC）水平显着低于那些具有PPAR α-11227A多态性的人。然而，在饮酒者中，V227 A多态性之间具有可比性，相反，当根据ALDH 2多态性进一步划分时，具有A227和醛脱氢酶2（ALDH 2）变体的人中更高。在总胆固醇、甘油三酯水平和AST/ALT比值方面，也发现了PPAR α-V227 A多态性和饮酒之间的显著相互作用。这些结果表明，A227等位基因的活性，而不饮酒可能高于野生型等位基因，但其活性可能会变得较低，在饮酒habites. ConclusionPPAR α-V227 A是一个主要的多态性在日本人口，其活性可能是更大的野生型相比，但降低饮酒。
Objectives Peroxisome proliferator-activated receptor (PPAR) a plays a major role in alcoholic liver disease in rodents. The two-fold objective of our study was to determine the presence of PPAR alpha polymorphisms and their frequencies in Japanese populations and then to evaluate the effects of any alleles on metabolic parameters and alcohol drinking.Methods Analysis of coding SNP in PPAR alpha was performed in 706 Japanese men; from these subjects 655 men were further studied after exclusion criteria were applied.Results PPAR alpha-V227A, which has not been reported in Europe and North America as a major polymorphism, was discovered with the frequency of 0.05. PPAR alpha-L162V was found in European and North American populations, but not in Japanese, thus confirming the ethnic differences in PPAR alpha allele frequencies. The A227 allele was associated with increased serum concentrations of gamma glutamyltranspeptidase. In non-drinkers, the total cholesterol (TC) levels were significantly lower in those having the PPAR alpha-11227A polymorphism. In drinkers, however, it was comparable among V227A polymorphisms, and conversely higher in those having both A227 and aldehyde dehydrogrenase 2 (ALDH2) variants when further divided according to the ALDH2 polymorphism. Significant interactions between PPAR alpha-V227A polymorphism and drinking were also found for TC, triglyceride levels and AST/ALT ratios. These results suggest that the activity of the A227 allele without drinking may be higher than in wild-type allele, but its activity may become lower during drinking habits.Conclusion PPAR alpha-V227A is a major polymorphism in the Japanese population, and its activity may be greater compared to wild-type, but decreased by alcohol drinking.