title: Genetic variation in the GCKR gene is associated with non-alcoholic fatty liver disease in Chinese people.
abstract: Recent genome-wide association studies reported that GCKR rs780094 polymorphism is associated with elevated fasting serum triglyceride levels and elevated levels of C-reactive protein (CRP). There are a ample of data on the association between circulating triglyceride, CRP concentrations and risk of non-alcoholic fatty liver (NAFLD). To determine whether the GCKR rs780094 polymorphism contributes to the development of non-alcoholic fatty liver, a case-control study was performed in 903 Chinese subjects. Among study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with steatosis hepatis I°, 90 with steatosis hepatis II° and 28 with steatosis hepatis III°) and 467 controls were genotyped by using TaqMan allelic discrimination assays. We confirmed the association of GCKR rs780094 with NAFLD in Chinese people (OR = 1.607, 95% CI 1.139-2.271, P[dom] = 7.2 × 10(-3)). In this study, polymorphism in GCKR rs780094 was not significantly associated with the degree of fatty infiltration of the liver. In addition, the T-allele of GCKR rs780094 was significantly associated with increasing fasting triglyceride (P[add] = 3.8 × 10(-4)) and CRP (P[add] = 2.9 × 10(-4)) concentrations after adjusting for age, gender, and BMI. The association with NAFLD remained significant after adjustment for triglyceride, while adjustment for CRP abolished the association. Genetic variation in GCKR gene rs780094 polymorphism contributes to the risk of NAFLD in Chinese people. The effect of genotype on NAFLD is probably mediated through chronic low-grade systemic inflammation rather than through dislipidemia.
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai Medical School, Fudan University, 12# Wulumuqi Middle Road, Shanghai, 200040, China. yangzhen1020@hotmail.com
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Tao
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Yanping
authors.initials: Y
authors.lastname: Du
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Xuanchun
authors.initials: X
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.forename: Songhua
authors.initials: S
authors.lastname: Wu
authors.forename: Renming
authors.initials: R
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000483:Alleles; D002097:C-Reactive Protein / Q000096:biosynthesis; D016022:Case-Control Studies; D002681:China; D005234:Fatty Liver / Q000208:ethnology / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485100:GCKR protein, human; D014280:Triglycerides; D002097:C-Reactive Protein