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Báo cáo y học: "Association of chemokine receptor gene (CCR2CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Association of chemokine receptor gene (CCR2CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians. | Malhotra et al. Retrovirology 2011 8 22 http www.retrovirology.eom content 8 1 22 RETROVIROLOGY RESEARCH Open Access Association of chemokine receptor gene CCR2-CCR5 haplotypes with acquisition and control of HIV-1 infection in Zambians Rakhi Malhotra1 Liangyuan Hu1 Wei Song1 Ilene Brill1 Joseph Mulenga3 Susan Allen3 4 Eric Hunter4 Sadeep Shrestha1 Jianming Tang2 and Richard A Kaslow1 2 Abstract Background Polymorphisms in chemokine C-C motif receptors 2 and 5 genes CCR2 and CCR5 have been associated with HIV-1 infection and disease progression. We investigated the impact of CCR2-CCR5 haplotypes on HIV-1 viral load VL and heterosexual transmission in an African cohort. Between 1995 and 2006 cohabiting Zambian couples discordant for HIV-1 index seropositive and HIV-1 exposed seronegative HESN were monitored prospectively to determine the role of host genetic factors in HIV-1 control and heterosexual transmission. Genotyping for eight CCR2 and CCR5 variants resolved nine previously recognized haplotypes. By regression and survival analytic techniques controlling for non-genetic factors we estimated the effects of these haplotypic variants on a index partner VL b seroconverter VL c HIV-1 transmission by index partners d HIV-1 acquisition by HESN partners. Results Among 567 couples 240 virologically linked transmission events had occurred through 2006. HHF 2 homozygosity was associated with significantly lower VL in seroconverters mean beta -0.58 log10 P 0.027 and the HHD HHE diplotype was associated with significantly higher VL in the seroconverters mean beta 0.54 log10 P 0.014 adjusted for age and gender in multivariable model. HHD HHE was associated with more rapid acquisition of infection by the HESNs HR 2.0 95 CI 1.20-3.43 P 0.008 after adjustments for index partner VL and the presence of genital ulcer or inflammation in either partner in Cox multivariable models. The HHD HHE effect was stronger in exposed females HR 2.1 95 CI 1.14-3.95 P 0.018 . Conclusions Among