APOBEC3H polymorphisms associated with the susceptibility to HIV-1 infection and AIDS progression in Japanese (original) (raw)

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.

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Acknowledgments

We are grateful Drs. Hanabusa H. (Ogikubo Hospital), Matsuda J. (Teikyo University School of Medicine), Sakai M. (University of Occupational and Environmental Health), Ikeda S. (Sasebo Municipal Hospital), and Fujii T. (Hiroshima University School of Medicine) for blood sampling from HIV-1-infected patients. This work was supported in part by research grants from the Ministry of Health, Labor and Welfare, Japan, and a Joint Research Program of National Hospital Organization Nagoya Medical Center, Japan.

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Authors and Affiliations

1. Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
   Daisuke Sakurai, Hitoshi Ohtani, Taeko K. Naruse & Akinori Kimura
2. Department of Infection and Immunology, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
   Yasumasa Iwatani & Wataru Sugiura
3. Biotherapy Institute of Japan, Tokyo, Japan
   Hiroshi Terunuma

Authors

1. Daisuke Sakurai
2. Yasumasa Iwatani
3. Hitoshi Ohtani
4. Taeko K. Naruse
5. Hiroshi Terunuma
6. Wataru Sugiura
7. Akinori Kimura

Corresponding author

Correspondence toAkinori Kimura.

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Sakurai, D., Iwatani, Y., Ohtani, H. et al. APOBEC3H polymorphisms associated with the susceptibility to HIV-1 infection and AIDS progression in Japanese.Immunogenetics 67, 253–257 (2015). https://doi.org/10.1007/s00251-015-0829-2

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• Received: 23 November 2014
• Accepted: 12 February 2015
• Published: 27 February 2015
• Issue Date: April 2015
• DOI: https://doi.org/10.1007/s00251-015-0829-2

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