RESUMO
BACKGROUND: Nasopharyngeal carcinoma (NPC), which occurs at a disproportionately high rate among Chinese individuals, is associated with Epstein-Barr virus (EBV). Human leukocyte antigen (HLA) polymorphisms appear to play a role in NPC, because they are essential in the immune response to viruses. We used high-resolution HLA genotyping in a case-control study in Taiwan to systematically evaluate the association between various HLA alleles and NPC. METHODS: We matched 366 NPC case patients to 318 control subjects by age, sex, and geographic residence. Participants were interviewed and provided blood samples for genotyping. High-resolution (polymerase chain reaction-based) genotyping of HLA class I (A and B) and II (DRB1, DQA1, DQB1, and DPB1) genes was performed in two phases. In phase I, 210 case patients and 183 control subjects were completely genotyped. In phase II, alleles associated with NPC in the phase I analysis were evaluated in another 156 case patients and 135 control subjects. Extended haplotypes were inferred. RESULTS: We found a consistent association between HLA-A*0207 (common among Chinese but not among Caucasians) and NPC (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5 to 3.5) but not between HLA-A*0201 (most common HLA-A2 allele in Caucasians) and NPC (OR = 0.79, 95% CI = 0.55 to 1.2). Individuals with HLA-B*4601, which is in linkage disequilibrium with HLA-A*0207, had an increased risk for NPC (OR = 1.8, 95% CI = 1.2 to 2.5) as did individuals with HLA-A*0207 and HLA-B*4601 (OR = 2.8, 95% CI = 1.7 to 4.4). Individuals homozygous for HLA-A*1101 had decreased risks for NPC (OR = 0.24, 95% CI = 0.13 to 0.46). The extended haplotype HLA-A*3303-B*5801/2-DRB1*0301-DQB1*0201/2-DPB1*0401, specific to this ethnic group, was associated with a statistically significantly increased risk for NPC (OR = 2.6, 95% CI = 1.1 to 6.4). CONCLUSIONS: The restriction of the association of HLA-A2 with NPC to HLA-A*0207 probably explains previously observed associations of HLA-A2 with NPC among Chinese but not Caucasians. The extended haplotypes associated with NPC might, in part, explain the higher rates of NPC in this ethnic group.
Assuntos
Alelos , Povo Asiático/genética , Carcinoma/genética , Genes MHC da Classe II , Genes MHC Classe I , Neoplasias Nasofaríngeas/genética , Adulto , Idoso , Carcinoma/imunologia , Estudos de Casos e Controles , Feminino , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/imunologia , Razão de Chances , TaiwanRESUMO
An increase in cervical intraepithelial neoplasia (CIN) has been described in American Indian women in New Mexico. Differences in human leukocyte antigen (HLA) alleles have been reported in cervical intraepithelial neoplasia (CIN) compared with controls in other populations. We investigated HLA alleles and CIN in Southwest American Indian women. The case control study included 89 women with biopsy-proven CIN II/III (diagnosed November 1994 through October 1997) and 271 similar women with normal cervical epithelium from the same clinics. DRB1, DQB1, and DPB1 alleles were determined using DNA typing techniques. DQA1 and HLA-A allele typing was included for some subjects (randomly chosen n = 37 and n = 163 cases and controls, respectively). We found a decreased risk of CIN with DRB1*1402 (OR 0.5, 95% CI 0.3-0.9) and an increased risk with DRB1*1501 (OR 2.7, 95% CI 0.9-7.3). Additionally, DQA1*0102 was associated with increased risk (OR 4.5, 95% CI 1.3-5.3) and HLA-A*02 with decreased risk (OR 0.4, CI 0.2-0.9). Our findings are discussed along with studies in other populations.
Assuntos
Antígenos HLA-A/genética , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-DP/genética , Cadeias beta de HLA-DP , Antígenos HLA-DQ/genética , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Humanos , Indígenas Norte-Americanos , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , New Mexico , Razão de Chances , Fatores de Risco , Neoplasias do Colo do Útero/etnologia , Neoplasias do Colo do Útero/patologiaRESUMO
Human leukocyte antigen A (HLA-A) genotypes were determined for samples from 283 multiplex, Caucasian, type 1 diabetes families from the Human Biological Data Interchange (HBDI) using an immobilized probe assay. Distribution of HLA-A alleles transmitted to patients was significantly different from that in affected family-based controls (AFBAC) (p = 0.004). Transmission disequilibrium test (TDT) analysis revealed differential transmission of several HLA-A alleles from parents to affected offspring. HLA class II DRB1 and DQB1 loci were also typed, allowing assignment of HLA-A alleles to haplotypes and calculation of linkage disequilibrium values. Some of the apparent effects of HLA-A alleles on type 1 diabetes susceptibility were attributable to linkage disequilibrium with DR and DQ alleles, although others were not. The differences in frequencies between patients and controls of alleles A*0101, A*2402, and A*3002 could not be explained by linkage disequilibrium alone. Our results suggest an important role for class I antigens in modulating susceptibility to type 1 diabetes.