血管紧张素Ⅱ1型受体基因rs3772622位点多态性与非酒精性脂肪性肝病发病风险的相关性分析

Association between AGTR1 gene polymorphism and risk of nonalcoholic fatty liver disease

目的探究血管紧张素Ⅱ1型受体（AGTR1）rs3772622位点多态性与非酒精性脂肪性肝病（NAFLD）的关系及该位点与patatin样磷酯酶域（PNPLA3）rs738409位点多态性的交互作用。方法选取2013年9月-2014年9月青岛市市立医院经临床B超诊断为NAFLD的患者241例及正常对照人群205例,采用PCR及基因型检测方法对AGTR1 rs3772622位点和PNPLA3 rs738409位点进行检测。运用统计学方法检测两位点等位基因频率、基因型频率及各项临床数据资料生化结果。计量资料行独立样本t检验,计数资料行χ2检验。通过二元Logistic回归分析AGTR1 rs3772622及PNPLA3 rs738409突变基因型罹患NAFLD的风险,使用广义多因子降维法（GMDR）研究两位点之间的交互作用。结果 AGTR1 rs3772622位点基因型及等位基因在NAFLD组与对照组中的分布频率差异无统计学意义（P〉0.05）。相对于野生型,AGTR1 rs3772622位点突变型并未增加NAFLD的发病风险（P〉0.05）,PNPLA3 rs738409突变型人群患NAFLD的风险是野生型的2.09倍[OR=2.09,95%可信区间（95%CI）：1.35~3.23,P=0.001]。AGTR1 rs3772622位点与PNPLA3 rs738409位点联合作用使NAFLD的发病风险明显增加（OR=3.60,95%CI：1.50~6.23,P〈0.001）。两突变基因双携带者与PNPLA3 rs738409单突变基因携带者生化指标的比较发现ALT、AST在两组间差异有统计学意义（P值均〈0.05）。结论中国人群中AGTR1 rs3772622位点多态性对NAFLD的发生发展无关。但其位点突变可增加PNPLA3rs738409位点突变患者罹患NAFLD的风险。

Objective To investigate the association between type 1 angiotensin II receptor（ AGTR1） rs3772622 polymorphism and nonalcoholic fatty liver disease（ NAFLD） and the interaction between the locus and patatin- like phospholipase domain- containing protein 3（ PNPLA3） rs738409 polymorphism. Methods A total of 241 patients who were diagnosed with NAFLD by B- mode ultrasound in Qingdao Municipal Hospital from September 2013 to September 2014 and 205 healthy controls were included. AGTR1 rs3772622 and PNPLA3rs738409 were determined by polymerase chain reaction and a genotyping method. A statistical analysis was performed on allele frequency,genotype frequency,and clinical / biochemical data of the two loci. According to different data types,t test and Pearson chi- square test were separately performed. The variant genotypes of AGTR1 rs3772622 and PNPLA3 rs738409 for risk of NAFLD were analyzed by Logistic regression analysis. The interactions between AGTR1 rs3772622 and PNPLA3 rs738409 were investigated by generalized multifactor dimensionality reduction. Results No significant differences were found between the NAFLD group and the control group as regards to the distribution of genotypes and alleles of AGTR1 rs3772622（ P〉 0. 05）. Compared with the wild type,the AGTR1 rs3772622 variant did not significantly increase the risk of NAFLD（ P〉 0. 05） and the variant carriers of PNPLA3 rs738409 had a 2. 09- fold increase in the risk of NAFLD [odds ratio（ OR） = 2. 09,95% confidence interval（ CI） ： 1. 35- 3. 23,P = 0. 001]. The combination of AGTR1 rs3772622 and PNPLA3rs738409 significantly increased the risk of NAFLD（ OR = 3. 60,95% CI： 1. 50- 6. 23,P 0. 001）. There were significant differences in alanine aminotransferase and aspartate aminotransferase between the single variant carriers of PNPLA3 rs738409 and the carriers of the two variants（ both P〈 0. 05）. Conclusion The polymorphism of AGTR1 rs3772622 is not associated with the development and progression of NAFLD in Chinese population,but the AGTR1 rs3772622 variant can increase the risk of NAFLD in variant carriers of PNPLA3 rs738409.