title: Association of Y chromosome haplogroup I with HIV progression, and HAART outcome.
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.
authors.affiliation: NCI-Frederick, MD 21702, USA.
authors.forename: Efe
authors.initials: E
authors.lastname: Sezgin
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Lind
authors.forename: Sadeep
authors.initials: S
authors.lastname: Shrestha
authors.forename: Sher
authors.initials: S
authors.lastname: Hendrickson
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: Sharyne
authors.initials: S
authors.lastname: Donfield
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.forename: John P
authors.initials: JP
authors.lastname: Phair
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Troyer
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Michael W
authors.initials: MW
authors.lastname: Smith
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000821:virology; D001741:Black or African American; D023241:Antiretroviral Therapy, Highly Active; D041322:Chromosomes, Human, Y / Q000235:genetics*; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000821:virology; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D044465:White People