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Diversity and Frequencies of HLA Class I and Class II Genes of an East African Population

Open Journal of Genetics 2014年第2期4卷 99-124页

作者： Trevor A. Peterson Thomas Bielawny philip lacap Rae-Anne Hardie Christina Daniuk Lillian Mendoza Subotheni Thavaneswaran Tony Kariri Joshua Kimani Charles Wachihi Maboku Kimani Terry Blake Ball Francis A. Plummer Ma Luo Department of Medical Microbiology University of Manitoba Winnipeg Canada Department of Medical Microbiology University of Nairobi Nairobi Kenya National Microbiology Laboratory Winnipeg Canada

Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.

关键词： HLA-A HLA-B HLA-C HLA-DPA1 HLA-DPB1 HLA-DQA1 HLA-DQB1 HLA-DRB1 HLA Frequencies HLA Class I HLA Class II East African

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