Genome-wide association scan in HIV-1-infected individuals identifying variants influencing disease course.

Autor: van Manen D; Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands., Delaneau O, Kootstra NA, Boeser-Nunnink BD, Limou S, Bol SM, Burger JA, Zwinderman AH, Moerland PD, van 't Slot R, Zagury JF, van 't Wout AB, Schuitemaker H
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2011; Vol. 6 (7), pp. e22208. Date of Electronic Publication: 2011 Jul 21.
DOI: 10.1371/journal.pone.0022208
Abstrakt: Background: AIDS develops typically after 7-11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (<2 years) and long-term non-progression (>15 years). To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS) in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS.
Methods: The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints.
Results: Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression.
Conclusions: Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection.
Databáze: MEDLINE
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