PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease

作     者：Quelson Coelho Lisboa Mateus Jorge Nardelli Patrícia de Araújo Pereira Débora Marques Miranda Stephanie Nunes Ribeiro Raissa Soares Neves Costa Camila Azevedo Versiani Paula Vieira Teixeira Vidigal Teresa Cristina de Abreu Ferrari Claudia Alves Couto 

作者机构：Departament de Clínica MédicaFaculty of MedicineUniversidade Federal de Minas GeraisBelo Horizonte 30130100Brazil 

出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)

年 卷 期：2020年第12卷第10期

页      面：792-806页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by Fundação de AmparoàPesquisa do Estado de Minas Gerais No.APQ-02233-14 

主　　题：Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Genetic variation Single nucleotide polymorphism Genotype Brazil Fibrosis 

摘      要：BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is becoming the most common chronic liver disease worldwide,with significant morbidity associated with nonalcoholic steatohepatitis(NASH).Genome-wide association studies demonstrated that the variants rs738409 C/G in the PNPLA3 and rs58542926 C/T in the TM6SF2 genes are determinants of inter-individual and ethnicity-related differences in hepatic fat content and NAFLD *** To investigate PNPLA3 and TM6SF2 genotype frequency and their association with NAFLD development and progression in Brazilian *** This cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in *** case patients(n=148)were confirmed to have NAFLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver *** to the clinical protocol,patients underwent liver biopsy when at high risk for NASH and/or advanced fibrosis(n=65).Steatohepatitis was confirmed in 54 *** who did not have biopsy indication or NASH on histology were considered to have simple steatosis(n=94).The control group(n=137)was selected among patients that attended the Intestinal Disease clinic and was composed of subjects without abnormalities on abdominal ultrasonography and normal liver biochemical *** individuals underwent PNPLA3 and TM6SF2 genotype *** PNPLA3 CC,CG and GG genotype frequencies were 37%,44%and 19%,respectively,in NAFLD patients and were 58%,31%and 10%in controls(P0.001).In a model adjusted for gender,age,body mass index and type 2 diabetes mellitus,the G allele increased the chance of NAFLD(OR=1.69,95%CI:1.21-2.36,P=0.002)and NASH(OR=3.50,95%CI:1.84-6.64,P0.001).The chance of NASH was even higher with GG homozygosis(OR=5.53,95%CI:2.04-14.92,P=0.001).No association was found between G allele and the features of metabolic *** histological assessment,PNPLA3 genoty