Abstract
The host genetic basis of differential outcomes in HIV infection, progression, viral load set point and highly active retroviral therapy (HAART) responses was examined for the common Y haplogroups in European Americans and African Americans. Accelerated progression to acquired immune deficiency syndrome (AIDS) and related death in European Americans among Y chromosome haplogroup I (Y-I) subjects was discovered. Additionally, Y-I haplogroup subjects on HAART took a longer time to HIV-1 viral suppression and were more likely to fail HAART. Both the accelerated progression and longer time to viral suppression results observed in haplogroup Y-I were significant after false-discovery-rate corrections. A higher frequency of AIDS-defining illnesses was also observed in haplogroup Y-I. These effects were independent of the previously identified autosomal AIDS restriction genes. When the Y-I haplogroup subjects were further subdivided into six I subhaplogroups, no one subhaplogroup accounted for the effects on HIV progression, viral load or HAART response. Adjustment of the analyses for population stratification found significant and concordant haplogroup Y-I results. The Y chromosome haplogroup analyses of HIV infection and progression in African Americans were not significant. Our results suggest that one or more loci on the Y chromosome found on haplogroup Y-I have an effect on AIDS progression and treatment responses in European Americans.
Original language | English (US) |
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Pages (from-to) | 281-294 |
Number of pages | 14 |
Journal | Human Genetics |
Volume | 125 |
Issue number | 3 |
DOIs | |
State | Published - 2009 |
Funding
Acknowledgments We thank the patients and staV of all the participating cohorts in the study. San Francisco City Cohort samples were provided by Susan Buchbinder. We thank Drs. George W. Nelson, James Lautenberger, Cheryl Winkler, Taras Oleksyk and Yvette Berthier-Schaad for helpful discussions. We are also grateful to Ann Truelove, Viktoriya Grinberg, Randy Johnson, Bailey Kessing, Michael Malasky, and Mary Thompson for their assistance. The content of this publication does not necessarily reXect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. The project described in this manuscript has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The HGDS is supported by 1 R01 HD41224, NIH/NCICHD.
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics