HLA‐G 3′ untranslated region polymorphisms influence the susceptibility for human papillomavirus infection

Abstract

Human leukocyte antigen (HLA)-G molecule acts as a potential factor for the regulation of immune responses and its expression in virus-infected cells may enable them to escape immunosurveillance. Besides its polymorphic promoter region, the 3' untranslated region (UTR) seems to play an important role in regulating HLA-G expression. In this study, we investigated the influence of HLA-G 14 bp (rs66554220) and +3142 (rs1063320) polymorphisms in 179 women with active human papillomavirus (HPV) infection and 143 age-matched, unrelated, HPV-negative, normal Chinese Han population. Our findings showed that frequency of the allele +3142 C [31.3% vs 44.4%, odds ratio (OR) = 0.57, Pc < 0.01] and the genotype +3142 CC (10.6% vs 21.7%, OR = 0.43, Pc = 0.012) was significantly decreased in HPV infected patients compared with normal controls. Furthermore, the haplotype -14 bp/C was associated with a reduced risk for HPV infection (OR = 0.57, Pc = 0.001). Our findings also showed that HLA-G homozygous +14 bp/+14 bp genotype was significantly associated with an increased risk for HPV18 infection (OR = 12.95, P < 0.01), whereas HLA-G heterozygous +14 bp/-14 bp genotype increased risk for HPV58 (OR = 5.55, P < 0.05). Furthermore, frequency of the haplotype +14 bp/G was significantly increased in HPV18 infected patients (60.0% vs 27.3%, OR = 4.00, Pc < 0.05). Taken together, our results supported a role of the HLA-G 3' UTR polymorphisms as a susceptible factor for the active HPV infection, and suggested a possible interference of the HLA-G molecule in the response to virus infection.

HLA-G Molecules in Autoimmune Diseases and Infections

“…There is also evidence to support also a role of HLA-G molecules in susceptibility and outcome of human papilloma virus (HPV) infections. The alleles HLA-G 14bp INS , + 1537C (rs12722477), G * 01:01, G * 01:04 , and G * 01:06 have been associated with both high-grade squamous intraepithelial lesions and cervical cancer, while HLA-G 14bp DEL and + 3142C alleles have been identified as protective ( 130 – 135 ). These results are in agreement with the low levels of HLA-G5 expression in cervical cancer ( 136 ).…”

Meta-analysis of correlationship between HLA-G 3′UTR 14-bp Ins/Del polymorphism and virus susceptibility

“…The specific characteristics of the qualified reports are presented in Table 1 . The included focused on the following virus types: hepatitis B virus (HBV), [ 11 , 15 , 16 ] HTLV-1, [ 9 , 10 ] human papillomavirus (HPV), [ 17 , 18 ] HCMV, [ 12 ] hepatitis C virus (HCV), [ 13 ] and human immunodeficiency virus (HIV). [ 14 ]…”

“…It is possible that the non-allelic interaction and host genes may be associated with persistence of virus infection. Xu et al [ 18 ] showed that the relationship between 14-bp Ins/+3142G haplotype and HPV18 infection risk was prominent in a previous study. In addition, higher frequency of the 14-bp Ins /+3142G haplotype was observed in African-derived HIV positive patients when compared with that in controls.…”

“…HLA-G is known as an important immune regulatory molecule that facilitates virus infection, and mediates tumor cell escape from host immunological surveillance by inhibiting immune cells functions. [ 18 ] Polymorphism of HLA-G 14-bp Ins/Del was shown to be associated with mRNA stability and splicing patterns, which may have an impact on the expression of HLA-G protein. [ 7 , 8 ]…”

“…[ 9 – 12 ] Other studies indicated that there is no association between HLA-G 14-bp Ins/Del polymorphism and virus infections. [ 13 – 18 ] Since these results were inconclusive, we decided to perform a systematic review to assess the relationship between HLA-G 14-bp Ins/Del polymorphism and virus infections.…”