title: Association of polymorphisms in human leukocyte antigen class I and transporter associated with antigen processing genes with resistance to human immunodeficiency virus type 1 infection.
abstract: To examine the relationship of human leukocyte antigen (HLA) class I and transporter associated with antigen processing (TAP) genes with resistance to human immunodeficiency virus type 1 (HIV-1) infection, 100 HIV-seronegative men who had been exposed repeatedly to HIV-1 were compared with 184 men who had seroconverted to HIV positive and had lower risk. In the univariate analysis, the HLA-A2 supertype, excluding A*0201 (HLA-A2/6802 supertype; odds ratio [OR], 4.45; 95% confidence interval [CI], 1.33-4.84; P=.009) was associated with resistance to HIV-1 infection; the effect was the result of the presence of the A*0205 subgroup alleles. Susceptibility was associated in univariate analysis with the B*35 Px alleles (OR, 0.29; 95% CI, 0.08-0.99; P=.037), which suggests that differential preferences for amino acids at the C terminus may influence peptide-binding capacity. TAP2 Ala665 was also associated with resistance (OR, 2.26; 95% CI, 1.35-3.79; P=.002), perhaps because of its higher efficiency in transporting peptides, thus eliciting a greater CD8(+) T cell response, or because of linkage disequilibrium. In multivariate logistic analysis, only the A*0205 subgroup (OR, 5.56; 95% CI, 1.34-23.10; P=.018) and the TAP2 Ala665 (OR, 2.22; 95% CI, 1.28-3.84; P=.005) were associated with resistance.
authors.affiliation: School of Public Health, University of California, Los Angeles, CA 90095, USA.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Liu
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: John
authors.initials: J
authors.lastname: Phair
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human