TY - JOUR
T1 - 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
AU - Liu, Chenglong
AU - Carrington, Mary
AU - Kaslow, Richard A.
AU - Gao, Xiaojiang
AU - Rinaldo, Charles R.
AU - Jacobson, Lisa P.
AU - Margolick, Joseph B.
AU - Phair, John
AU - O'Brien, Stephen J.
AU - Detels, Roger
N1 - Funding Information:
Financial support: National Institute of Allergy and Infectious Diseases (NIAID) and National Cancer Institute (grants UO1-AI-35042, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041 to MACS); NIAID (grant 5-MO1-RR-00722 to the General Clinical Research Center); National Institutes of Health (contract NO1-CO-12400).
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
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U2 - 10.1086/374394
DO - 10.1086/374394
M3 - Article
C2 - 12717621
AN - SCOPUS:0038555813
SN - 0022-1899
VL - 187
SP - 1404
EP - 1410
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -