Allele HLA-DQB1*06 reduces fibrosis score in patients with non-alcoholic fatty liver disease.

Abstract

Human leukocyte antigen (HLA) regions were highlighted as important genetic markers for various liver diseases by hepatology-related genome-wide association studies. Replication studies in non-alcoholic fatty liver disease (NAFLD) are limited and none has investigated the association of HLA alleles with non-alcoholic steatohepatitis (NASH) and other histological characteristics. In the current study, we examined the association of HLA-DQA1 and HLA-DQB1 alleles with NAFLD spectrum and its histological characteristics. Consecutive biopsy-proven NAFLD patients (n= 191) and healthy controls (n= 188) were enrolled and genotyped for HLA-DQA1 and HLA-DQB1 alleles using the sequence-specific oligonucleotide-polymerase chain reaction method. No association was found between the HLA alleles and NAFLD or NASH in a case-control setting. Nevertheless, among NAFLD patients, the frequency of HLA-DQB1*06 allele was significantly the lowest in NASH with significant fibrosis (10.4%) and approximately similar for NASH without significant fibrosis (22.9%) and NAFL (22.5%) (P=0.004). It is noteworthy that the association remains significant after correction for multiple comparisons (Pc = 0.04). Multivariate analysis revealed that HLA-DQB1*06 allele is also associated with fibrosis score (P = 0.001); the result remains significant after correction for multiple comparisons. These findings suggest that HLA-DQB1*06 is associated with lower fibrosis score in NAFLD patients.