The HLA‐G 14 bp insertion/deletion polymorphism is a putative susceptible factor for active human cytomegalovirus infection in children

Abstract

Human leukocyte antigen-G (HLA-G) expression is a potential factor for the pathogenesis of virus infection. A 14 bp insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene is involved in the stability of HLA-G mRNA and HLA-G protein expression. Therefore, the HLA-G 14 bp polymorphism might be involved in human cytomegalovirus (hCMV) infection. To test a possible association between the HLA-G 14 bp deletion/insertion polymorphism and the active hCMV infection, in this study, a total of 54 patients with active hCMV infection and 165 age- and sex-matched, unrelated, normal Chinese Han population were genotyped for the 14 bp insertion/deletion polymorphism. Association of 14 bp polymorphism with hCMV urine DNA copies and the odds ratio (OR) of the polymorphism as a risk factor for active hCMV infection were analyzed. Our results showed that the prevalence of -14 bp/ -14 bp genotype in active hCMV patients was markedly increased [P(c) = 0.00034, OR = 3.31, 95% confidence interval (CI): 1.77-6.18], and similar significance was also observed for the frequency of -14 bp allele (P c = 0.0023, OR = 2.24, 95% CI: 1.38-3.64) when compared with that of healthy controls. Furthermore, urine hCMV DNA copies in patients with the -14 bp/ -14 bp genotype were significantly higher than those in patients with the +14 bp/ +14 bp genotype (P = 0.041). Our findings support a potential role of HLA-G 14 bp insertion/deletion polymorphism as a susceptible factor for the active hCMV infection.

Genetic Factors Influence Serological Measures of Common Infections

“…Infection with T. gondii has been associated with genes encoding interferon gamma, tolllike receptors, and the purinergic receptor P2X 7 [41][42][43] . CMV susceptibility is attributed in part to polymorphisms in several genes including those encoding cytokines, toll-like receptors, and other immune response molecules [34,44,45] . Alterations in the HLA region and polymorphisms in genes encoding cytokines are linked to EBV susceptibility [46,47] .…”

Analysis of the plasma soluble human leukocyte antigen–G and interleukin-10 levels in childhood atopic asthma

“…Studies indicated that the polymorphism was associated with HLA-G mRNA stability and isoform alternative splicing pattern and influences protein expression level of HLA-G [14 -16]. The significance of this polymorphism association with many disorders, such as human cytomegalovirus infection, human immunodeficiency virus (HIV) vertical transmission, systemic lupus erythematosus, and idiopathic dilated cardiomyopathy have also been addressed [17][18][19][20].…”

Can immune-related genotypes illuminate the immunopathogenesis of cytomegalovirus disease in human immunodeficiency virus–infected patients?

“…Upregulation of these molecules on NK cell lines has been associated with overexpression of HLA-G, which may facilitate immune evasion [10]. Homozygous carriage of the 14-base pair (bp) deletion polymorphism in HLA-G has been associated with susceptibility to CMV disease [12].…”