Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions

被引:0
|
作者
Xuelin Li
Matthew A. Price
Dongning He
Anatoli Kamali
Etienne Karita
Shabir Lakhi
Eduard J. Sanders
Omu Anzala
Pauli N. Amornkul
Susan Allen
Eric Hunter
Richard A. Kaslow
Jill Gilmour
Jianming Tang
机构
[1] University of Alabama at Birmingham,Department of Medicine
[2] International AIDS Vaccine Initiative,Department of Epidemiology and Biostatistics
[3] UCSF,Department of Epidemiology
[4] University of Alabama at Birmingham,Centre for Geographic Medicine Research
[5] MRC/UVRI Uganda Virus Research Unit on AIDS,Centre for Clinical Vaccinology and Tropical Medicine
[6] Projet San Francisco,Department of Pathology and Laboratory Medicine
[7] Zambia-Emory HIV-1 Research Project,Vaccine Research Center
[8] Kenya Medical Research Institute (KEMRI),International AIDS Vaccine Initiative, Human Immunology Laboratory
[9] University of Oxford,undefined
[10] Kenya AIDS Vaccine Initiative (KAVI),undefined
[11] Emory University,undefined
[12] Emory University,undefined
[13] Chelsea and Westminster Hospital,undefined
[14] Department of Veterans Affairs,undefined
来源
Human Genetics | 2014年 / 133卷
关键词
Viral Load; Human Leukocyte Antigen; Human Leukocyte Antigen Class; Human Leukocyte Antigen Allele; Human Leukocyte Antigen Genotyping;
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摘要
Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P < 0.0001) but not in men (frequency = 7.7 %, P = 0.66). This novel sex by HLA interaction (P = 0.003, q = 0.090) did not extend to other frequent HLA class I alleles (n = 34), although HLA-C*18:01 also showed a weak association with low VL in women only (frequency = 9.3 %, P = 0.042, q > 0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P < 0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of “missing heritability” in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations.
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页码:1187 / 1197
页数:10
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