Comprehensive analysis of HFE gene in hereditary hemochromatosis and in diseases associated with acquired iron overload

作     者：Wagner Narciso de Campos Juliana Doblas Massaro Eduardo Luiz Rachid Can?ado Cláudia Emília Vieira Wiezel Aguinaldo Luiz Sim?es Andreza Correa Teixeira Fernanda Fernandes de Souza Celso Teixeira Mendes-Junior Ana de Lourdes Candolo Martinelli Eduardo Ant?nio Donadi 

作者机构：Division of Clinical ImmunologyDepartment of MedicineRibeir?o Preto Medical SchoolUniversity of S?o Paulo Department of GastroenterologyClinical Gastroenterology and Clinical Hepatology of Clinical HospitalUniversity of S?o Paulo School of Medicine Department of GeneticsRibeir?o Preto Medical SchoolUniversity of S?o Paulo Division of GastroenterologyDepartment of MedicineRibeir?o Preto Medical SchoolUniversity of S?o Paulo Departamento de QuímicaLaboratório de Pesquisas Forenses e Gen?micasFaculdade de FilosofiaCiências e Letras de Ribeir?o PretoUniversidade de S?o Paulo 

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

年 卷 期：2019年第11卷第2期

页      面：186-198页

学科分类：10[医学] 

基　　金："Conselho Nacional de Desenvolvimento Cientifico e Tecnologico"(CNPq Brazil) No.304931/2014-1 and No.148638/2010-4 

主　　题：HFE gene Hepatocellular carcinoma Hepatitis C Hemochromatosis hereditary Alleles Haplotypes 

摘      要：BACKGROUND Patients with hepatitis C virus(HCV) and hepatocellular carcinoma(HCC) may or not develop iron overload(IO),which is associated with worst prognosis,because can cause serious damage to *** gene controls the iron uptake from gut,particularly in patients with hereditary hemochromatosis(HH).AIM To identify associations between HFE coding region in patients exhibiting hereditary hemochromatosis and in diseases associated with acquired *** We sequenced exons 2 to 5 and boundary introns of HFE gene,evaluating all polymorphic sites in patients presenting hereditary(hemochromatosis) or acquired iron overload HCV and HCC) and in healthy controls,using Sanger *** also determined the ensemble of extended haplotype in healthy control individuals,including several major histocompatibility complex loci,using sequence specific *** reconstruction was performed using the Arlequin and Phase softwares,and linkage disequilibrium(LD) between histocompatibility loci and HFE gene was performed using the Haploview *** The HFE*003 allele was overrepresented(f = 71%) and HFE*001 allele was underrepresented(f = 14%) in HH patients compared to all groups.A strong linkage disequilibrium was observed among the H63 D-G,IVS2(+4)-C and C282 YG gene variants,particularly in HH;however,the mutation IVS2(+4)TC was not directly associated with HH *** HFE*001/HFE*002 genotype conferred susceptibility to HCC in HCV patients exhibiting IO(P = 0.02,OR =14.14).Although HFE is telomeric to other histocompatibility genes,the H63 DG/IVS2(+4)-C(P ≤ 0.00001/P ≤ 0.0057) combination was in LD with HLA-B*44 allele group in healthy *** LD was observed between HFE alleles and other major histocompatibility *** A differential HFE association was observed for HH and for diseases associated with acquired IO(HCV,HCC).Since HFE is very distant from other histocompatibility loci,only weak associations were observed with these a