Association of Y chromosome haplogroup I with HIV progression, and HAART outcome.
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.
Sezgin
Efe
E
NCI-Frederick, MD 21702, USA.
Lind
Joanne M
JM
Shrestha
Sadeep
S
Hendrickson
Sher
S
Goedert
James J
JJ
Donfield
Sharyne
S
Kirk
Gregory D
GD
Phair
John P
JP
Troyer
Jennifer L
JL
O'Brien
Stephen J
SJ
Smith
Michael W
MW
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