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Biology Faculty Articles
Title
Fraction of Cases of Acquired Immunodeficiency Syndrome Prevented by the Interactions of Identified Restriction Gene Variants
Document Type
Article
Publication Date
2-1-2004
Publication Title
American Journal of Epidemiology
Keywords
Acquired immunodeficiency syndrome, Chemokines, Cytokines; Epidemiologic methods, HIV-1, HLA antigens, Receptors, Chemokine
ISSN
0002-9262
Volume
159
Issue/No.
3
First Page
232
Last Page
241
Abstract
Previous research has demonstrated isolated effects of host genetic factors on the progression of human immunodeficiency virus type 1 (HIV-1) infection. In this paper, the authors present a novel use of multivariable methods for estimating the prevented fraction of acquired immunodeficiency syndrome (AIDS) cases attributable to six restriction genes after accounting for their epidemiologic interactions. The methods presented will never yield a prevented fraction above 1. The study population consisted of a well-characterized cohort of 525 US men with HIV-1 seroconversion documented during follow-up (1984–1996). On the basis of a regression tree approach using a Cox proportional hazards model for times to clinical AIDS, the combinations of genes associated with the greatest protection, relative to the lack of a protective genotype, consisted of: 1) C-C chemokine receptor 5 (CCR5)-Δ32 and C-C chemokine receptor 2 (CCR2)-64I (relative hazard = 0.44); 2) interleukin 10 (IL10)-+/+ in combination with CCR5-Δ32 or CCR2-64I (relative hazard = 0.45); and 3) IL10-+/+ in combination with stromal-derived factor (SDF1)-3′A and CCR5 promoter P1/~P1 (relative hazard = 0.37). Overall, 30% of potential AIDS cases were prevented by the observed combinations of restriction genes (95% confidence interval: 7, 47). However, the combined effect was confined to the first 4 years following HIV-1 seroconversion. Additional research is needed to identify AIDS restriction genes with stronger and long-lasting protection to better characterize the genetic epidemiology of HIV-1.
Additional Comments
National Cancer Institute grant and contract #s: UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, NO1-CO-12400
NSUWorks Citation
Silverberg, M. J.; M. W. Smith; Joan S. Chmiel; Roger Detels; Joseph Margolick; Charles Rinaldo; Stephen J. O'Brien; and A. Muñoz. 2004. "Fraction of Cases of Acquired Immunodeficiency Syndrome Prevented by the Interactions of Identified Restriction Gene Variants." American Journal of Epidemiology 159, (3): 232-241. https://nsuworks.nova.edu/cnso_bio_facarticles/578
ORCID ID
0000-0001-7353-8301
ResearcherID
10.1093/aje/kwh036
Comments
©2004 by the Johns Hopkins Bloomberg School of Public Health