HLA-DRB1 Class II antigen level alleles are associated with persistent HPV infection in Mexican women; a pilot study

Abstract

BackgroundPersistent infection with high-risk human papillomavirus (HPV) is a major risk factor for malignant lesions and cervical cancer. A widely studied element in the search for genetic factors influencing risk HPV infection diseases is allelic variation of the human leukocyte antigen (HLA) locus. The study was designed to search for HLA susceptibility alleles contributing to the persistence of HPV infection in Mexican women.MethodsA total of 172 subjects were divided into three groups: 1) HPV–persistent patients; 2) HPV–cleared; and 3) HPV–reinfected patients. They were screened for HPV types using a polymerase chain reaction (PCR). PCR-sequence specific oligonucleotide probes (PCR-SSOP) was used for HLA DRB1 and DQB1 typing.ResultsWe observed that HLA-DQB1*0501 allele might be associated with susceptibility of reinfection with HPV (p = 0.01, OR = 4.9, CI 95% = 1.3 -18.7). Allele frequency of HLA-DRB1*14 was particularly reduced in patients with cancer when compared with the HPV–persistent group (p = 0.04), suggesting that this allele is a possible protective factor for the development of cervical cancer (OR = 2.98). HLA-DRB1*07 might be associated with viral clearance (p = 0.04).ConclusionsGenetic markers for HPV infection susceptibility are different in each population, in Mexicans several HLA-DQB1 alleles might be associated with an enhanced risk for viral persistence. In contrast, DRB1*14, seems to confer protection against cervical cancer.

Identifying the HLA DRB1-DQB1 molecules and predicting epitopes associated with high-risk HPV infection clearance and redetection

“…The alleles/haplotypes favourably associated with viral clearance and hindering redetection could have been related to a lower risk of CC (given the lower risk of infection and viral persistence), whilst associations hindering clearance and favouring redetection www.nature.com/scientificreports www.nature.com/scientificreports/ could have been related to a greater risk of CC (greater risk of infection and persistence). Previous cohort results (regarding just infection by HPV-16 and -18) would seem to support such inferences and the results presented here (Supplementary Tables S12 to S15) [19][20][21][22] .…”

HLA Allele and Haplotype Frequencies in Three Urban Mexican Populations: Genetic Diversity for the Approach of Genomic Medicine

“…Another allele associated with autoimmune diseases is HLA-A*01:01, which has been associated with the development of psoriatic arthritis in the Chinese population [43]. In a pilot study in the Mexican population, HLA-DQB1*05 was associated with susceptibility of reinfection with human papillomavirus [44]. Two alleles (HLA-DRB1*03:01 and DRB1*04:04) that we found in greater proportions in our study have been conferred with an increased risk of Addison's disease [45].…”

In-silico analysis of MHC genes in hereditary colorectal cancer shows identical by state SNP sharing affecting HLA-DQB1 binding groove

“…The role of MHC in colorectal cancer is not well understood. HLA variants have been linked to many types of malignancies including cervical, lung, breast and other malignancies [5][6][7][8][9].…”

“…Epstein-Barr virus, Human Papilloma Virus) show HLA-related predisposition or protection. Bernel-Silva et al found that HLA-DRB1*14 allele seems to confer protection against cervical cancer [5]. However, other types of cancer with no clear relation to infectious agents show HLA predisposition as well.…”