PNPLA3基因与非酒精性脂肪性肝病发生发展相关性研究  

Correlation of the PNPLA3 Gene with Non-alcoholic Fatty Liver Disease

作　　者：钱建成[1] 金燕[1] 罗燕[2] 施军平[2] 

机构地区：[1]浙江省立同德医院感染科,杭州310012 [2]杭州师范大学附属医院转化医学平台,杭州310015

出　　处：《浙江中西医结合杂志》2016年第7期607-611,I0001,I0002,共7页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

摘　　要：目的分析中国成人非酒精性脂肪性肝病(NAFLD)患者PNPLA3基因多态性与肝脏损害的相关性,探讨遗传因素在中国成人NAFLD发生和发展中的作用。方法连续收集106例NAFLD患者和100名年龄、性别相匹配的健康人。用测序分型法和Taqman探针分型法分别测定所有纳入者rs738409、rs2281135的单核苷酸多态性(SNP)。同时测定患者肝功能(ALT、AST、GGT)、空腹血糖(FBG)、空腹胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,以及血压、身高、体质量、体质量指数(BMI);用稳态模型评估法计算胰岛素抵抗指数(HOMA-IR)。结果 rs738409突变纯合型GG型NAFLD组(40.6%)高于健康对照组(13.0%),CC型则NAFLD组(17.9%)低于健康对照组(44.0%),差异有统计学意义(P<0.05),携带等位基因G的NAFLD患者CG/GG组较CC组具有更高谷丙转氨酶(ALT)[(82.03±61.25)U/L比(53.84±38.78)U/L,P<0.05]、谷氨酰转肽酶(GGT)[(83.66±52.92)U/L比(56.42±34.02)U/L,P<0.01];rs2281135突变纯合型AA型NAFLD组(24.5%)高于健康对照组(15.0%),野生GG型则NAFLD组(26.4%)低于健康对照组(44.0%),差异有统计学意义(P<0.05),携带突变基因A的患者较GG纯合子具有更高ALT[(85.52±61.63)U/L比(53.18±32.62)U/L、GGT[(84.08±54.21)U/L比(64.00±37.85)U/L,差异具有统计学意义(P<0.05)。结论 PNPLA3 rs738409和rs2281135多态性与NAFLD遗传易感性有显著相关性;PNPLA3 rs738409等位基因G和rs2281135等位基因A可增加肝损害(ALT、GGT)的风险,且与胰岛素抵抗无相关性。Objective To analyze the correlation of adult non-alcoholic fatty liver disease（NAFLD） patients＇ PNPLA3 gene polymorphism with liver damage, and to explore the genetic factors in the occurrence and development in Chinese NAFLD patients. Methods Hundred and six patients with NAFLD and 100 age- and sex-matched healthy people were continuously collected in this study. Sequencing typing method and Taqman probe typing method were used to measure the single nucleotide polymorphism（SNP） of rs738409, rs2281135 in subjects.Subjects＇ liver function（ALT, AST, GGT）, fasting blood glucose（FBG）, fasting insulin（FINS）, total cholesterol（TC）,triglyceride（TG）, high density lipoprotein cholesterol（HDL-C）, and low-density lipoprotein cholesterol（LDL-C） levels were determined and blood pressure, height, weight, body mass index（BMI） were measured; homeostasis model assessment insulin resistance index（HOMA-IR） was calculated. Results The PNPLA3 rs738409 genotype GG was observed in 40.6% patients of NAFLD group and in 13.0% healthy subjects; the genotype CC was observed in17.9% patients of NAFLD group and in 44.0% healthy subjects, both with a significant difference（P〈0.05）. Patients carrying the G allele（CG/GG） in NAFLD group had significant higher levels of ALT and GGT compared with pa tients with CC genotype（ALT： 82.03±61.25U/L vs 53.84±38.78U/L and GGT： 83.66±52.92U/L vs 56.42±34.02U/L;all P〈0.05）. The PNPLA3 rs2281135 mutant genotype AA was observed in 24.5% patients in NAFLD group and in15.0% healthy subjects; the GG type was observed in 26.4% patients in NAFLD group and in 44.0% healthy subjects, both with a significant difference（P〈0.05）. Patients carrying the A allele in NAFLD group had higher levels of ALT and GGT compared with patients with GG homozygotes with a statistically significant difference（ALT：85.52±61.63U/L vs 53.18±32.62U/L and GGT： 84.08±54.21U/L vs 64.00 ±37.85U/L; all P〈0.05）. Conclusion PNPLA3 rs738409 and rs2281135 pol

关 键 词：非酒精性脂肪性肝病 PNPLA3 单核苷酸多态性 

分 类 号：R575[医药卫生—消化系统]