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Abstract: Background: Genetic variants of the genes encoding HIV-1 co-receptors and their ligands, CCR5-Δ32, CCR5m303A, CCR2-64I and SDF1-3′A, are implicated in the susceptibility to HIV-1 infection, and the prevalence of these mutations varies by ethnicity. However, little is known about their distribution in Uighurs. Objectives: This study aimed at characterizing the frequency of these HIV-related gene variants in a high-risk Uighur population. Study designs: A total of 251 HIV-1 seropositive and 238 seronegative high-risk Uighurs were recruited and their genotypes of CCR5-Δ32, CCR5m303A, CCR2-64I and SDF1-3′A were analyzed by PCR and PCR-ligase detection reaction (PCR-LDR). Results: The allelic frequency of CCR5-Δ32, CCR5m303A, CCR2-64I and SDF1-3′A was 4.40%, 2.66%, 25.66% and 57.36%, respectively, in this population. Apparently, the Uighur population has low frequency of CCR5-Δ32 and CCR5m303A, but high frequency of CCR2-64I and SDF1-3′A. While there was no significant difference in the frequency of CCR5-Δ32, CCR2-64I and SDF1-3′ A between HIV-1 seropositive and seronegative groups the frequency of CCR5m303A in HIV-1 seropositive group was significantly higher than that in seronegative group (P =0.006, OR=3.982 and 95%CI 1.514–10.476). Conclusions: Our data suggest that the CCR5-Δ32, CCR2-64I and SDF1-3′A variants may have limited effect on protecting from HIV-1 infection in Uighurs. Rather, the CCR5m303A may be associated with the risk for HIV-1 infection in high-risk Uighurs. [Copyright &y& Elsevier]