HLA-Cw*0409N is associated with HLA-A*2301 and HLA-B*4403-carrying haplotypes.

The associations of HLA-B4402 and HLA-B4403 with alleles of HLA-A and HLA-Cw were investigated in panels of HLA-B4403 and HLA-B4402 homozygous individuals and in selected individuals carrying HLA-Cw04 and HLA-B4403. Some of these individuals were genotyped and also carried (HLA-DRB10701, DQB102). Among the latter, we studied individuals carrying the conserved extended haplotype (CEH) [HLA-Cw04, B4403, FC31, DRB10701, DQB102]. Four different common (HLA-Cw*, B44) haplotypes were identified that extended to the HLA-A locus: HLA-A0201, Cw0501, B4402; HLA-A2902, Cw1601, B4403; HLA-A2301, Cw0401, B4403; and HLA-A2301, Cw0409N, B4403. We identified eight unrelated examples of the allele HLA-Cw0409N. HLA-A2301 was associated with both HLA-Cw0401 and HLA-Cw0409N, suggesting that HLA-Cw0409N may have arisen from a mutation in a CEH. We estimate that approximately 2 to 5 in 1000 Caucasian individuals carry the allele HLA-Cw0409N, making it one of the most frequent null HLA alleles known to date. Our findings demonstrate the first example of three different HLA-Cw-determined subtypes of a common or CEH carrying a shared HLA-B allele, in this case HLA-B4403.