HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus

Abstract

Human papillomavirus (HPV) infection is etiologically associated with low-(LSIL) and high-grade squamous intraepithelial lesions (HSIL) and with cervical cancer. The progression or regression of the lesions may depend, among other factors, on the host heritable immune response. Because human leukocyte antigen (HLA)-G molecules are involved in the modulation of innate and adaptive immune responses, and because no previous studies have evaluated HLA-G polymorphism in patients with SIL, we conducted a study to assess the association between HLA-G polymorphisms and cervical lesions harboring HPV infection. Cervico-vaginal scrapings and blood samples were collected from 125 women with SIL (68 LSIL and 57 HSIL) and from 94 healthy women without HPV infection and cytological abnormalities. HPV type and HLA-G polymorphisms in exons 2, 3 and 8 (14 bp insertion/deletion) were evaluated by PCR methodology, and digested with restriction endonucleases. The Genepop software and the EM and PHASE algorithms were used for statistical analysis. A significant protective association was observed between the presence of the G*0103 allele and SIL and between the G0101/G0104 genotype and HSIL in the group of patients compared to control. The presence of the G0104/ þ 14 bp and G0104/À14 bp haplotypes conferred susceptibility to SIL compared to control. In addition, patients possessing the G0104/ þ 14 bp haplotype and harboring HPV-16 and -18 co-infections were particularly associated with HSIL. These findings suggest that HLA-G polymorphisms may be associated with HPV infection and SIL, consequently representing a profile of predisposition to cervical cancer.

Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix

“…23 Simões et al recently reported that patients possessing the extended HLA-G*01:04/ 14-bp insertion haplotype and harboring HPV-16 and À18 co-infections were particularly susceptible to HG-CIN lesions. 24 Although HPV infection is a necessary intermediate step in cervical carcinogenesis 1 and the large majority of preinvasive and invasive cervical lesions was HPV-positive, none of the HLA-G alleles was associated with risk of HPV infection per se among controls. The HLA-G*01:01:02 allele associated with risk of HPV-induced invasive cancer was previously found to increase risk of infection with HPV-16 type, 12 however, the authors were unable to detect an association between this allele and HPV infection in the control group.…”

Cervix smear abnormalities: linking pathology data in female twins, their mothers and sisters

“…Different polymorphic human leukocyte antigen genes might be involved in the clearance and maintenance of HPV infection and a TP53 gene allele (codon-72) might be associated with susceptibility to HPVassociated cervical carcinogenesis. [27][28][29] An association between the glutation S-transferase mu 1 null genotype and cervical cancer was reported in an US population 30 and a Japanese population. 31 Both the risk of HPV infection and the risk to develop cervical cancer are associated with lifestyle factors; for example, the use of oral contraceptives, smoking, education, physical activity, high parity, risky sexual behavior, multiple sexual partners and previous exposure to other sexually transmitted diseases.…”

HLA-E, HLA-F and HLA-G — The Non-Classical Side of the MHC Cluster

“…This allele is characterized by a nonsynonymous C-T mutation at codon 142 in exon 3. HLA G* 01:01:08 was a rare allele in most populations with exception of Brazil (8 and 15%), Zimbabwe (6%), and Poland (5%) (Simoes et al, 2009;SipakSzmigiel et al, 2008). This allele is characterized by a nonsynonimous G-A mutation at codon 57 in exon 2.…”