Diversity is demonstrated in class I HLA‐A and HLA‐B alleles in Cameroon, Africa: description of HLA‐A*03012, *2612, *3006 and HLA‐B*1403, *4016, *4703

Abstract

To examine the genetic diversity in west Africa, class I HLA-A and HLA-B alleles of 92 unrelated individuals from two areas in the Cameroon, the capital Yaoundé and the village of Etoa, were identified by direct automated DNA sequencing of exons 2 and 3 of the HLA-B locus alleles and sequence-specific oligonucleotide probe (SSOP) and/or sequencing of the HLA-A locus alleles. HLA-A*2301 (18.7%), A*2902 (10.4%), B*5301 (10.9%), and B*5802 (10.9%) were the most frequently detected alleles, present in at least 10% of the population. A total of 30 HLA-A locus and 33 HLA-B locus alleles, including six novel alleles, were detected. The novel alleles were HLA-A*03012, A*2612, A*3006 and HLA-B*1403, B*4016, and B*4703. HLA-B*4703 contains a novel amino acid sequence that is a combination of the first 5 amino acids of the Bw6 epitope and the last 2 residues of the Bw4 epitope. The addition of 6 alleles to the ever-expanding number of known class I HLA alleles supports our hypothesis that extensive genetic diversity, including previously undescribed alleles, would be observed in this African population. In the Yaoundé population, the allele frequency distribution at the HLA-A locus is consistent with distributions indicative of balancing selection. Extensive HLA-A-B haplotypes were observed in this population suggesting that only a fraction of the Cameroon HLA-A-B haplotype diversity has been observed.

Association of ankylosing spondylitis with HLA–B*1403 in a West African population

“…The positive association of AS with B*1403 has not previously been described in either of the populations examined. This is of considerable interest, since this allele has been described as a rare subtype that is underrepresented in the population of Cameroon (11). We also detected the presence of B*1404 in 1 AS patient, but this association needs to be confirmed in additional population studies.…”

Two HLA-B14 Subtypes (B*1402 and B*1403) Differentially Associated with Ankylosing Spondylitis Differ Substantially in Peptide Specificity but Have Limited Peptide and T-cell Epitope Sharing with HLA-B27

“…Recently, B*1403, an allotype reported only in the African populations of Cameroon and Togo (16,17), was found strikingly associated to AS in the Togolese population, where both this disease and HLA-B27 are rare (17). Of 7 HLA-B27-negative AS patients that could be clinically and genetically evaluated, 4 (57%) were of the B*1403 allotype.…”

Disparate folding and stability of the ankylosing spondylitis–associated HLA–B*1403 and B*2705 proteins

“…HLA-B*1403 is found almost exclusively in subSaharan African (23,24) and African American populations (25,26), with a prevalence of Ͻ1%. In sub-Saharan Africa, AS is also very uncommon (27).…”