AUTHOR=Wang Xiaoliang , Liu Zhipeng , Wang Kai , Wang Zhaowen , Sun Xing , Zhong Lin , Deng Guilong , Song Guohe , Sun Baining , Peng Zhihai , Liu Wanqing 

TITLE=Additive Effects of the Risk Alleles of PNPLA3 and TM6SF2 on Non-alcoholic Fatty Liver Disease (NAFLD) in a Chinese Population

JOURNAL=Frontiers in Genetics

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2016.00140

DOI=10.3389/fgene.2016.00140

ISSN=1664-8021

ABSTRACT=<p>Recent genome-wide association studies have identified that variants in or near <italic>PNPLA3, NCAN, GCKR, LYPLAL1</italic>, and <italic>TM6SF2</italic> 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) (<italic>PNPLA3</italic> rs738409, rs2294918, <italic>NCAN</italic> rs2228603, <italic>GCKR</italic> rs780094, <italic>LYPLAL1</italic> rs12137855, and <italic>TM6SF2</italic> 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, <italic>PNPLA3</italic> rs738409 (OR = 1.52, 95%CI: 1.19–1.96; <italic>P</italic> = 0.00087) and <italic>TM6SF2</italic> rs58542926 (OR = 2.11, 95%CI: 1.34–3.39; <italic>P</italic> = 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 <italic>PNPLA3</italic> and <italic>TM6SF2</italic> with an overall significance between the number of risk alleles and NAFLD (OR = 1.64, 95%CI: 1.34–2.01; <italic>P</italic> = 1.4 × 10<sup>-6</sup>). The OR for NAFLD increased in an additive manner, with an average increase in OR of 1.52 <italic>per</italic> additional risk allele. Our results confirmed that the <italic>PNPLA3</italic> and <italic>TM6SF2</italic> 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.</p>