Novel Polymorphism in the Promoter Region of HLA-DQB1 Is a Predictor of Anti-HCV Therapy Response

Jundishapur Journal of Microbiology

Muhammad Arshad¹  Abida Raza²  Ismail Jalil³ 

[1] Department of Microbiology, Quaid-i-Azam University, Islamabad, Pakistan;Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University, Islamabad, Pakistan;National Institute of Laser and Optronics, Pakistan Atomic Energy Commission Islamabad, Pakistan

关键词: Novel Polymorphism in the Promoter Region of HLA-DQB1 Is a Predictor of Anti-HCV Therapy Response;    Hepatitis;    Polymorphisms;    SNPs;    TNF-α;    HLA-DRB1;    HLA-DQB1;    Haplotypes;   

DOI  :  10.5812/jjm.92217

学科分类：微生物学和免疫学

来源: Jundishapur Journal of Microbiology

【 摘 要 】

Hepatitis C virus (HCV) is a major cause of chronic liver infection, which may lead to liver cirrhosis, fibrosis, and hepatocellular carcinoma while about one-fourth of the infected patients recover spontaneously. The host immune response remains decisive in the outcomes of antiviral treatment. Single nucleotide polymorphisms (SNPs) at the genes within the human leukocyte antigen (HLA) cluster are associated with differential immune response and treatment outcomes.This study aimed to determine the association of SNPs in Tumor necrosis factor-alpha (TNF-α) and HLA genes (HLA-DRB1 and HLA-DQB1) with the outcomes of HCV infection and anti-HCV therapy.The study included 245 HCV-infected patients visiting a tertiary care hospital, located in Islamabad, Pakistan. Viral quantification and genotyping were performed by real-time PCR. Twenty SNPs in TNF-α, HLA-DRB1, and HLA-DQB1 were sequence-genotyped by the Sanger method in 180 patients. Multivariate logistic regression was performed to establish the association of SNPs with spontaneous clearance of the virus and response to anti-HCV therapy.Five out of 20 SNPs were novel. Allelic variants at three different locations (HLA-DRB1, rs2308802; HLA-DQB1,-8447, and HLA-DQB1,-8471) showed significant associations with two groups of HCV patients receiving anti-HCV treatment (responsive and non-responsive). Multivariate analyses disclosed that genotype A/A at HLA-DQB1 (-8471) was a significant predictor of positive response to treatment although in the presence of the variant at HLA-DRB1 (rs230880) (P = 0.004). However, no association was detected between the haplotypes constructed for the three sets of SNPs and different categories of patients. This study established a novel SNP HLA-DQB1(-8471) as an important predictor of an effective response to anti-HCV therapy in HCV-infected Pakistani patients. Prescreening of this variant before therapy would benefit HCV patients.

【 授权许可】

CC BY-NC