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We analysed GCH1 in symptomatic HIV-associated sensory neuropathy (HIV-SN) in Southern Africans including a ‘pain protective’ 3-SNP haplotype and 6 SNPs, analysed individually and in a 6-SNP haplotype. The ‘pain protective’ 3-SNP haplotype and a 6-SNP haplotype containing these alleles associated with a reduced risk of pain. Another 3-SNP haplotype associated with increased presence of pain. Associations were lost after correction for age, gender and CD4 T-cell count. Linkage disequilibrium differed between our cohort and Caucasians suggesting that these SNPs may not be ideal markers in Africans. Subsequently the role of GCH1 in painful HIV-SN remains possible.