HLA‐G polymorphism influences the susceptibility to HCV infection in sickle cell disease patients

Abstract

Despite its well known monogenic etiopathogenesis, sickle cell disease (SCD) is characterized by a striking variability of clinical presentation. There is growing evidence that genetic factors may be involved in this variability. Human leukocyte antigen (HLA)-G is a non-classical HLA molecule which was shown to be expressed at sites of inflammation and in inflammatory diseases. Besides its large and highly polymorphic promoter region, the 3' UTR region seems also to play an important role on regulating HLA-G expression. We investigated the influence of the 14 pb (rs1704) and the +3142 (rs1063320) HLA-G polymorphisms in 93 SCD patients in order to evaluate its potential role on clinical parameters. Twenty-one patients presented an HCV infection. Among all SCD patients 16 (22.2%) were homozygous for the +3142C genotype, none of them hepatitis C (HCV) positive. Controlling for blood transfusions in the last year, the C allele represented a dose dependent protection effect for HCV infection (PR = 0.41; 95% CI: 0.24-0.71). The +3142C allele was also underrepresented among patients with history of respiratory-tract infections. Our results support a role of the +3142 polymorphism in the susceptibility to infections, in particular to HCV infection, and suggest a possible interference of the HLA-G molecule in the response to infections, among SCD patients.

Elevation of plasma soluble human leukocyte antigen–G in patients with chronic hepatitis C virus infection

“…Roles of HLA-G expression induced by influenza A virus [21], human cytomegalovirus virus (HCMV) [22], human immunodeficiency virus (HIV) [23], HBV [24], and rabies virus [25] have been discussed. Recently, Cordero et al found that HLA-G polymorphism ϩ3142 (rs1063320) could influence the susceptibility to HCV infection in patients with sickle cell disease [26]; however, expression of HLA-G and its role in HCV infection are unknown.…”

Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection

“…Previous studies revealed that polymorphic sites at the 3= untranslated region of the HLA-G gene, which are potentially associated with the magnitude of HLA-G production, have been associated with risk factors for the vertical transmission of HCV [13] and susceptibility to HCV infection in sickle cell disease patients [14]. Recently, Weng et al reported that plasma soluble HLA-G levels were dramatically altered in individuals with chronic HCV infection; however, expression of HLA-G in live and its role in HCV infection remain unknown [15].…”

The pharmacogenetic background of hepatitis C treatment

“…Certain genotypes of the human leukocyte antigen (HLA) confer an increased susceptibility to infection or favor spontaneous viral clearance [30][31][32][33]. Early studies using normalization of ALT levels for six months after treatment end to define SVR found a positive association after interferon-monotherapy with HLA-DR2 in Egyptians (OR 9.495 [34]) and DRB1*0404 in Caucasians (DRB1*0404+: SVR = 25% vs. DRB1*0404À: SVR = 2.3% [35]).…”