Associations of human leucocyte antigen class II‐DQB1 alleles with hepatitis C virus infection in Egyptian population: a multicentre family‐based study

Abstract

Hepatitis C infection is a global pandemic. HLA-DQB1 alleles are believed to have an effective role in immune response against HCV including susceptibility to or protection from this infection. The aim of this study was to investigate the contribution of HLA-DQB1 alleles in the outcome of HCV genotype-4 infection through a family-based association study. Egyptian families with HCV (324) were recruited for this study (324 index positive for RNA-HCV, 225 positive relatives representing chronic hepatitis C cases and 582 family members negative for HCV-RNA [control], 63 of whom spontaneously cleared the virus. All subjects were genotyped for HLA-DQB1 alleles by sequence-specific primers (SSP-PCR) and sequence-based typing (SBT) methods. The frequency of DQB1*02:01:01 carriage was significantly higher in infected patients when compared to controls and those who spontaneously cleared virus (OR=5.47, P<.0001 and OR= 6.5234, P<.0001, respectively), and the carriage of the DQB1*03:01:01:01 allele was significantly higher in those who cleared and controls when compared to the infected patients (OR=0.2889, P<.0001 and OR=0.3016, P<.0001, respectively). On the other hand, the frequency of DQB1*06:01:01 and QB1*05:01:01:01 alleles was not associated with infection (comparison of infected and cleared patients showed OR of 2.1598 [P<.01]), but it becomes nonsignificant after adjustments with the Bonferroni formula (P >0.05) and OR= 1.3523, P>.05, respectively. This study shows that clearance of HCV is associated with DQB1*03:01:01:01 allele and chronicity of HCV infection associated with the risk allele: DQB1*02:01:01.

Semen quality is affected by HLA class I alleles together with sexually transmitted diseases

“…Concerning HLA‐DQB1*03:01 allele, identified as a risk factor for OLI, previous studies showed conflicting results: Whereas in chronic hepatitis, this allele has been correlated in some instances with HCV clearance (Huang et al ., ; Thio et al ., ; El‐Bendary et al ., ), other authors have reported a link between HLA‐DQB1*03:01 and HPV6 infection (Chen et al ., ). Notably, this HPV subtype, despite being considered as low risk for cervical cancer, is established to cause genital lesions and to be found in the semen (Lyu et al ., ; Flores‐Díaz et al ., ).…”

“…Importantly, several alleles of HLA class I and II genes have already been correlated with sexually transmitted diseases (STD) caused by Neisseria gonorrhoeae (gonorrhea) (Ness et al ., ; Geisler et al ., ), Chlamydia trachomatis (Ness et al., ; Olson et al., ), Treponema pallidum (syphilis) (Zhuang et al ., ; Jiang et al ., ), human immunodeficiency virus (HIV) (Raghavan et al ., ; Rallón et al ., ), human papillomavirus (HPV) (Chen et al ., ), hepatitis B virus (HBV) (Nishida et al ., ), and hepatitis C virus (HCV) (Huang et al ., ; Thio et al ., ; El‐Bendary et al ., ). Such microbial agents per se and together with activated immunological processes can lead to anatomical obstruction, compromise normal gland function, affect the availability of diverse seminal components, and interfere in sperm viability (du Plessis et al ., ; Flint et al ., ; Weidner et al ., ; Gimenes et al ., 2014a; Bezold et al ., ).…”

The relationship between human leukocyte antigen-DP/DQ gene polymorphisms and the outcomes of HCV infection in a Chinese population

“…Previous research has shown that low viral diversity and strong CD4+ T-cell response targeting a broad range of virus antigenic epitopes are connection with spontaneous viral clearance (SVC), while infectious agents can lead to incompetent T-cell response and persistent infection through a variety of complex mechanisms [ 28 ]. Furthermore, the epitopes of CD4+ T-cell are highly promiscuous and can often be restricted by a variety of different HLA class II molecules [ 29 ].…”

The association of LMP7 and TAP2 gene polymorphisms with treatment response to interferon/ribavirin in patients with genotype 1 chronic hepatitis C

“…MHC class I and II antigens are the central to the host immune response, which make them ideal candidate genes to investigate their association with HCV infection (18). HLA is a crucial genetic factor that initiates and regulates immune response through presenting endogenous and exogenous antigen to T lymphocytes (12). An increased and broadly multi-specific T-cell response is critical to get a favorable outcome.…”

“…A genetic association study clarified that the human leukocyte antigen (HLA) was an essential genetic factor that regulated immune response and may be one of the tactics used by HCV to avoid immune clearance (12). Furthermore, various HLA alleles involved in the immune response were demonstrated to be linked to spontaneous clearance of HCV infection and even be potentially predictive for HCV treatment response (13).…”