13th International AIDS Conference Durban, South Africa - July 9-July 14, 2000

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA342)

Ramaley PA, French N, Kaleebu P, Gilks CF, Whitworth J, Hill AV;;; P.A. Ramaley, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom, Tel.: +44 1865 287 592, Fax: +44 1865 287 660, E-mail: pramaley@well.ox.ac.uk

BACKGROUND: The host genetics of HIV-1 infection and disease progression has been intensively investigated in Caucasians but there have been few studies of sub-Saharan Africans. It is unknown whether polymorphisms which impact HIV-1 disease in Western populations will also play a similar role, or even be present, in Africans.

METHODS: Two cohorts were investigated: a rural population of 271 HIV+ cases and 270 controls in the Masaka district and a peri-urban population of 1149 cases and 330 controls in Entebbe. Collection of samples was done in the rural group as part of a multidisciplinary surveillance program and in Entebbe as part of a pneumococcal pneumonia vaccine trial. Microsatellite markers, insertion/deletions, and single nucleotide polymorphisms were genotyped by oligonucleotide hybridization, RFLP or ligation detection reaction after PCR.

RESULTS: Polymorphisms in several genes failed to show any significant association with either infection or disease progression: SDF-1, haptoglobin, CCR-2, RANTES and ICAM-1. In Entebbe the -592 C allele in the promoter of the interleukin-10 gene was associated with increased susceptibility to HIV-1 infection (P = 0.01). This allele has been reported to be associated with increased IL-10 expression. No effect of IL-10 polymorphism on disease progression was found. In both Entebbe and Masaka district a relatively uncommon 9-bp deletion in exon 2 of the natural resistance associated macrophage protein-1 (NRAMP1) gene, that removes three amino acids from a SH3-binding domain of NRAMP1, was consistently associated with susceptibility to HIV-1 infection (Masaka, p = 0.01; Entebbe, p = 0.01).

CONCLUSIONS: In these East African populations different genetic association with HIV-1 infection and disease progression are observed compared to reported data from Caucasians.

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