Multiple low-frequency and rare HLA-B allelic variants are associated with reduced risk in 1,105 nasopharyngeal carcinoma patients in Hunan province, southern China
| Autor: | LiXin Li, Wen Yi Wang, Fa Ming Zhu, Wei Tian, Jin Hong Cai, He Kun Jin |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Cancer Research Linkage disequilibrium China Locus (genetics) Human leukocyte antigen Biology 03 medical and health sciences 0302 clinical medicine Gene Frequency medicine Genetic predisposition Odds Ratio Humans Genetic Predisposition to Disease Allele Alleles Genetics Nasopharyngeal Carcinoma HLA-A Antigens Haplotype Nasopharyngeal Neoplasms Middle Aged medicine.disease HLA-B Oncology Nasopharyngeal carcinoma Haplotypes HLA-B Antigens 030220 oncology & carcinogenesis Mutation Female |
| Zdroj: | International journal of cancerReferences. 147(5) |
| ISSN: | 1097-0215 |
| Popis: | In our study, 1,105 cases of nasopharyngeal carcinoma (NPC) and 1,430 normal controls recruited from Hunan province, southern China were typed for human leukocyte antigen (HLA)-B locus by Sanger sequencing exons 2-4. Besides confirming the NPC association with HLA-B*46:01 allele, HLA-A*02:07-B*46:01 and HLA-A*33:03-B*58:01 haplotypes (all positive), and HLA-B*13 lineage (negative), all of which were relatively common, strong negative associations were observed for five low-frequency and rare alleles or lineages, including HLA-B*07, -B*27:04, -B*39, -B*51:02 and -B*55:02, with odds ratio (OR) ranging from 0.16 to 0.3 (all pcorrected < 0.05). These strong protective associations were independent of linkage disequilibrium (LD) between HLA-A and HLA-B loci. Further analysis indicated a single amino acid change from histidine to tyrosine at residue 171 is probably crucial for the mutant allele, HLA-B*51:02, to mediate resistance to NPC. A subset of NPC cases (n = 821) and normal controls (n = 1,035) were tested for antivirus capsid antigen immunoglobulin A (anti-VCA IgA), which differed drastically between the two groups [67.7% vs. 5.5%, OR (95% confidence interval) = 36 (26.55-48.81), p < 0.0001]. HLA-B allelic variation did not associate with seropositivity for anti-VCA IgA in either group. Results from our study show, more clearly than previously, the existence of a cluster of low-frequency and rare HLA-B variants conferring low, or very low risk to NPC, a phenomenon not observed in other ethnic groups. Our data shed new insights into genetic susceptibility to NPC in southern Chinese populations. Future independent studies are warranted to replicate the findings reported in our study. |
| Databáze: | OpenAIRE |
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