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

• 作者: Camila Azevedo Versiani Claudia Alves Couto Débora Marques Miranda Mateus Jorge Nardelli Patrícia de Araújo Pereira Paula Vieira Teixeira Vidigal Quelson Coelho Lisboa Raissa Soares Neves Costa Stephanie Nunes Ribeiro Teresa Cristina de Abreu Ferrari
• 来源期刊: 世界肝病学杂志:英文版(电子版)
• 学科: 医学
• 关键词: Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Genetic variation Single nucleotide polymorphism GENOTYPE Brazil FIBROSIS
• 年，卷（期）: 2020,（10）
• 页码范围: 792-806
• 页数: 15页
• 分类号: R57

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 progression.AIM To investigate PNPLA3 and TM6SF2 genotype frequency and their association with NAFLD development and progression in Brazilian patients.METHODS This cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in Brazil.The case patients(n=148)were confirmed to have NAFLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver disease.According 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 patients.Individuals 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 tests.All individuals underwent PNPLA3 and TM6SF2 genotype analysis.RESULTS PNPLA3 CC,CG and GG genotype frequencies were 37%,44%and 19%,respectively,in NAFLD patients and were 58%,31%and 10%in controls(P<0.001).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,P<0.001).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 syndrome.In histological assessment,PNPLA3 genotype was not associated with steatosis grade,altho