NEW TAP2 POLYMORPHISMS IN AFRICANS

Polymorphisms in genes encoding transporters associated with antigen p rocessing (TAP) have been associated with heterogeneity of disease pro gression in HIV-1-infected homosexual men. In our recent AIDS-related studies of cohorts from Rwanda and Zambia, four new polymorphic sites in the TAP2 coding region were detected by single-strand conformation polymorphism (SSCP) and confirmed by bi-directional nucleotide sequenc ing and restriction enzyme digestion. The first, a substitution of Thr (GCC) for Ala of (ACC) at codon position 374 in exon 5, was found in about 13% of Rwandans and Zambians (n=213). The remaining 3 new polymo rphisms were seen in the 7th exon with changes of 458Thr-ACG to ACA, 4 66Gly-GGG to GGA, and 467Val-GTT to Ile-ATT, respectively. These 3 var iants occurred exclusively on the same chromosome and appeared to have arisen together from the 374Thr-bearing allele. Analyses of the relat ionship between the 374Thr-467IIe segment and the nearby markers in DQ B1 and DRB1 suggested the existence of a unique extended haplotype rel ated to these newly identified variants.