title: Additive Effects of the Risk Alleles of PNPLA3 and TM6SF2 on Non-alcoholic Fatty Liver Disease (NAFLD) in a Chinese Population.
abstract: Recent genome-wide association studies have identified that variants in or near PNPLA3, NCAN, GCKR, LYPLAL1, and TM6SF2 are significantly associated with non-alcoholic fatty liver disease (NAFLD) in multiple ethnic groups. Studies on their impact on NAFLD in Han Chinese are still limited. In this study, we examined the relevance of these variants to NAFLD in a community-based Han Chinese population and further explored their potential joint effect on NAFLD. Six single nucleotide polymorphisms (SNPs) (PNPLA3 rs738409, rs2294918, NCAN rs2228603, GCKR rs780094, LYPLAL1 rs12137855, and TM6SF2 rs58542926) previously identified in genome-wide analyses, to be associated with NAFLD were genotyped in 384 NAFLD patients and 384 age- and gender-matched healthy controls. We found two out of the six polymorphisms, PNPLA3 rs738409 (OR = 1.52, 95%CI: 1.19-1.96; P = 0.00087) and TM6SF2 rs58542926 (OR = 2.11, 95%CI: 1.34-3.39; P = 0.0016) are independently associated with NAFLD after adjustment for the effects of age, gender, and BMI. Our analysis further demonstrated the strong additive effects of the risk alleles of PNPLA3 and TM6SF2 with an overall significance between the number of risk alleles and NAFLD (OR = 1.64, 95%CI: 1.34-2.01; P = 1.4 × 10(-6)). The OR for NAFLD increased in an additive manner, with an average increase in OR of 1.52 per additional risk allele. Our results confirmed that the PNPLA3 and TM6SF2 variants were the most significant risk alleles for NAFLD in Chinese population. Therefore, genotyping these two genetic risk factors may help identify individuals with the highest risk of NAFLD.
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN USA.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Children's Hospital of Zhengzhou, Zhengzhou China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Xing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Guilong
authors.initials: G
authors.lastname: Deng
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Guohe
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Geriatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Baining
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN USA.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Liu
keywords: Chinese; NAFLD; PNPLA3; TM6SF2; additive effects