MICA EXON 5 SHORT TANDEM REPEAT POLYMORPHISM AND HLA HAPLOTYPES IN ZAMBIANS.

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MICA EXON 5 SHORT TANDEM REPEAT POLYMORPHISM AND HLA HAPLOTYPES IN ZAMBIANS.
Elena S. Lobashevsky, MD, PhD , M. Tevfik Dorak MD, PhD , Jianming Tang PhD , Shenghui Tang PhD , Isaac Zulu MD, MPH , Susan Allen MD, MPH and Richard A. Kaslow, MD, PhD . Birmingham AL, University of Alabama at Birmingham, 35294, Epidemiology and Birmingham AL, University of Alabama at Birmingham, 35294, Zambia UAB HIV Research Project (ZUHRP) .

The MHC class I-like locus MICA, located 46kb from HLA-B, encodes a stress-induced cell surface molecule involved in NK cell biology and probably transplant immunology. Its polymorphisms in exon 2-4, and the exon 5 short tandem repeat (STR) variants have been studied in Caucasians but not in other populations. As the initial approach to study MICA polymorphisms in an African population, we typed the exon-5 STR in 286 Zambian individuals already typed at HLA-A, B, Cw and DRB1. Typing was performed on ALFexpress DNA Analyzer (Amersham Biosciences). The results were analyzed on SAS and EH software for two- and three-locus linkage disequilibrium (LD), respectively. The commonest alleles A9 and A6 were each present in more than 50% of individuals. The commonest Caucasian allele A5.1 had a marker frequency of 47.3% (allele frequency = 27.2%). The strongest LD between MICA and HLA-B was noted between these three alleles and the four most frequent HLA-B alleles: HLA-B*53 - A9 (Δ = 0.061), HLA-B*58 - A9 (Δ = 0.056), B*42 - A6 (Δ = 0.060) and B*15 (mostly *1503) - A5.1 (Δ = 0.065) with P < 0.0001. Among the three-locus B-MICA-DRB1 haplotypes, the only African ancestral haplotype 42.1 (B*4201-MICA*A6-DRB1*0302) showed an extraordinary level of LD (Δ = 0.061; P < 10^-10). Other common three-locus haplotypes with significant LD (Δ > 0.01) were: B*15-MICA*5.1-DRB1*11; B*53-MICA*9-DRB1*10. Most of these LD patterns are not seen in Caucasians because of the unique HLA-B alleles in Zambians. Neither of these extended haplotypes occurs in Caucasians at high frequencies. Documentation of unique MICA and HLA alleles and haplotypes in Zambians should help delineate the extended haplotypes and their role in infectious diseases like HIV/AIDS in Africa.