TRIM5α has species-specific restriction activity against replication of many retroviruses, including HIV-1. Though human also express TRIM5α protein, it is less potent in suppressing infection of HIV-1 than most orthologs of other nonhuman primates. Previous association studies suggested that polymorphisms in TRIM5α gene might protect against HIV-1 infection. However, the exact variation accounting for this protective effect was not certain.
One thousand two hundred ninety-four Chinese intravenous drug users (IDUs), including 1011 Hans and 283 Dai subjects, were investigated for sequence variations in TRIM5α and association with HIV-1 resistance. Resequencing of the putative functional domains in exon2 and exon8 was carried out in 1151 subjects, along with exon2 resequencing in a further 143 HIV-1-infected IDUs.
We identified 14 different nucleotide variants, including 4 with minor allele frequency >0.05. We observed that the frequency of 43Y homozygote in seronegative IDUs was significantly higher than that in the HIV-1-infected IDUs, suggesting a protective effect among the homozygote subjects [odds ratio (95% confidence interval) = 0.46 (0.22 to 0.94), P = 0.033, Mantel-Haenszel test].
we concluded that H43Y might account for the HIV-1 resistance due to TRIM5α gene in Chinese IDUs.
From the *Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; †KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, Yunnan, China; ‡Graduate School of Chinese Academy of Sciences, Beijing, China; §Departments of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; ‖Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, China; and ¶Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Received for publication April 15, 2010; accepted October 25, 2010.
Supported by National Basic Research Program of China (2006CB504302, 2006CB504208, 2009CB522306), National Natural Science Foundation of China (30671960, U0832601, 30872317, 30800113), the Knowledge Innovation Program of CAS (KSCX2-YW-R-185), and Eleventh Five-Year Key Scientific and Technological Program of China (2008ZX10001-002, 2008ZX10001-015, 2009ZX10004-902, 2008ZX10005-005, 2009ZX09501-029).
The authors have no conflict of interest to disclose.
Correspondence to: Nelson Leung Sang Tang, MD, Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China (e-mail:firstname.lastname@example.org) or Yong-Tang Zheng, PhD, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China (e-mail: email@example.com).