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Genomics Day 2005: Genomics Day 2005: Public Health Genomics at CDC

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Group 1: Genetics and Immunity

Association of CCR5 promoter human haplogroup E with faster HIV-1 disease progression among injection drug users (IDU) in Thailand
Nguyen L¹, Li M¹, Chaowanachan T², Hu DJ¹, Vanichseni S³, Mock PA², Van Griensvena F², Martin M ¹,², Sangkum U⁴, Choopanya C³, Tappero JW¹,², Lal RB¹, and Yang C¹.
(1) CDC
(2) Thai MOPH-U.S. CDC Collaboration
(3) Bangkok Vaccine Evaluation Group, Thailand
(4) Bangkok Metropolitan Administration, Thailand

 

Objective: An evolutionary-based analysis of the CC chemokine receptor 5-gene (CCR5) promoter region identified nine stable human haplogroups (HHs). Within the nine, certain haplogroups appear to influence HIV-1 disease progression differentially among Caucasians and African-Americans. We assessed the influence of CCR5 haplogroups on HIV-1 disease progression in a Thai population.

Design: We examined HIV-1 seropositive injection drug users (IDUs) participating in a prospective cohort study in Bangkok . All IDUs were documented seroconverters with a median follow-up time of 3.5 years (range: 0.2 to 7.0 years).

Methods: From a cohort of 130 IDUs, we genotyped 106 (81.5%) participants for the CCRb2-64I,CCR5- D 32 and seven CCR5 promoter alleles constituting the CCR5 haplogroups. Survival curves and adjusted Cox proportional hazards models were used to assess the effect of haplogroups on the time from HIV-1 infection until CD4 count <200 cells/ m L.

Results: The most common CCR5 haplogroups were HHC (61.8%), followed by HHE (15.6%) and HHF*2 (14.6%). The HHE was associated with an accelerated CD4+ T-cell decline to <200 cell/µL (adjusted RH: 1.88; CI (95%): 1.05-3.36, P = 0.02).

Conclusions: Our data provide the first evidence that the CCR5 haplogroup E speeds the decline of CD4 and may lead to accelerated disease progression among HIV-infected Thais. These new observations highlight the need for additional studies involving populations in Asia.