Polymorphisms of interleukin-1β and β3-adrenergic receptor in Japanese patients with nonalcoholic steatohepatitis
Polymorphisms of interleukin-1β and β3-adrenergic receptor in Japanese patients with nonalcoholic steatohepatitis
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DOI：
10.1097/01.alc.0000134410.42980.5e
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发表时间：
2004-08-01
影响因子：
3.2
通讯作者：
Onishi, S
中科院分区：
文献类型：
--
作者：
Nozaki, Y;Saibara, T;Onishi, S
背景：据报道，肥胖、高甘油三酯血症和糖尿病是西方国家非酒精性脂肪性肝炎 (NASH) 患者常见的并发症。本研究的目的是调查日本人群 NASH 发病机制的遗传倾向。方法：使用聚合酶链反应和限制性片段长度多态性，在 63 名日本 NASH 患者和 100 名健康志愿者中确定了两种先前描述的功能性多态性蛋白的基因型，即导致 Trp64Arg (W64R) 氨基酸替换的 β3-肾上腺素受体 190 T/A 多态性和启动子序列中的白介素-1β-511 T/C 多态性。结果：NASH 患者的 β3 肾上腺素受体 R 等位基因频率和 R/-（W/R 和 R/R）基因型频率显着高于对照组。 NASH 患者的 Interleukin-1beta-511 T 等位基因频率和 T/T 基因型频率显着高于对照组。肥胖、高甘油三酯血症和高胰岛素血症与 R/- 基因型 NASH 患者相关，而空腹血糖水平升高和胰岛素生成指数降低与 W/W 基因型 NASH 患者相关。结论：这项研究证实了肥胖、葡萄糖不耐受和高甘油三酯血症对日本人群 NASH 发展的影响。除了这些因素外，日本人群的肥胖和炎症遗传倾向也被证明对 NASH 的发展有很大影响。
Background: Obesity, hypertriglyceridemia, and diabetes have been reported as frequent complications observed in patients with nonalcoholic steatohepatitis (NASH) in Western countries. The aim of this study was to investigate the genetic predisposition on NASH pathogenesis in the Japanese population. Methods: Genotypes of two previously described functional polymorphisins-beta3-adrenergic receptor 190 T/A polymorphism, which results in Trp64Arg (W64R) amino acid replacement, and interleukin-1beta-511 T/C polymorphism in the promoter sequence-were determined in 63 Japanese NASH patients and 100 healthy volunteers using polymerase chain reaction and restriction fragment length polymorphism. Results: beta3-adrenergic receptor R allele frequency and the R/- (W/R and R/R) genotype frequency were significantly higher in NASH patients than those in control subjects. Interleukin-1beta-511 T allele frequency and the T/T genotype frequency were significantly higher in NASH patients than those in control subjects. Obesity, hypertriglyceridemia, and hyperinsulinemia were associated with NASH patients with the R/- genotype, whereas an increase in fasting plasma glucose level and a decrease in insulinogenic index were associated with NASH patients with the W/W genotype. Conclusion: This study confirmed the contribution of obesity, glucose intolerance, and hypertriglyceridemia to NASH development in the Japanese population. In addition to these factors, genetic predispositions to obesity and inflammation in the Japanese population were shown to contribute much to the development of NASH.