title: APOBEC3H polymorphisms associated with the susceptibility to HIV-1 infection and AIDS progression in Japanese.
abstract: Human APOBEC3H (A3H) is a member of APOBEC3 cytidine deaminase family that potently restricts HIV-1 replication. Because A3H is genetically divergent with different intracellular stability and anti-HIV-1 activity in vitro, we investigated a possible association of A3H with susceptibility to HIV-1 infection and disease progression in Japanese populations. A total of 191 HIV-1-infected individuals (HIV group), 93 long-term non-progressors to AIDS (LTNP group) and 421 healthy controls were genotyped for two functional APOBEC3H polymorphisms, rs139292 and rs139297. As compared with the controls, minor allele frequency (MAF) for rs139292 was high in the HIV group (MAF in cases vs. controls; 0.322 vs. 0.263, odds ratio (OR) = 1.33, 95% confidence interval (95% CI) = 1.02-1.74, p = 0.035) and low in the LTNP group (0.161 vs. 0.263, OR = 0.54, 95% CI = 0.36-0.82, p = 0.004, pc = 0.007), whereas the MAF for rs139297 was high in the HIV group (0.367 vs. 0.298, OR = 1.36, 95% CI = 1.07-1.76, p = 0.017, pc = 0.035). In addition, haplotype analyses revealed that the frequencies of A3H-hapC and -hapA were high (0.322 vs. 0.262, OR = 1.33, 95% CI = 1.02-1.74, p = 0.003) and low (0.634 vs. 0.697, OR = 0.75, 95 % CI = 0.58-0.97, p = 0.002), respectively, in the HIV group, whereas the frequencies of A3H-hapC and -hapB were low (0.161 vs. 0.262, OR = 0.54, 95% CI = 0.36-0.82, p = 0.00003) and high (0.097 vs. 0.040, OR = 2.55, 95% CI = 1.40-4.62, p = 0.000008), respectively, in the LTNP group, as compared with those in the controls. These observations suggest that the A3H with low anti-HIV-1 activity, A3H-hapC, is associated with the susceptibility to HIV-1 infection, whereas the A3H producing a stable protein, A3H-hapB, may confer a low risk of disease progression to AIDS.
authors.affiliation: Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakurai
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Iwatani
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohtani
authors.forename: Taeko K
authors.initials: TK
authors.lastname: Naruse
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Terunuma
authors.forename: Wataru
authors.initials: W
authors.lastname: Sugiura
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology* / Q000276:immunology; D000619:Aminohydrolases / Q000235:genetics*; D018450:Disease Progression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D014779:Virus Replication / Q000235:genetics*
chemical_list: C529313:APOBEC3H protein, human; D000619:Aminohydrolases