Sixteen HLA-DRB1 haplotype classification system

A haplotype is a combination of genetic variations occurring together (on the same DNA strand). The combination of amino acids at HLA-DRB1 positions 11/13, 71, and 74 defines 16 haplotypes and allows the classification of healthy individuals of northern European descent in 16 strata based on their risk to develop RA when healthy or based on their risk to develop a severe form of RA when the disease has developed. HLA-DRB1 positions 11 and 13 are always inherited together in populations of northern European descent and are therefore interchangeable (one codon at position 11 will automatically determine which codon is present at position 13). Based on HLA-DRB1 positions 11/13, 71, and 74, only 16 different haplotypes exist within the White population and only 8 of these are frequent (occurring in more than 5% of the population; indicated in bold). This table presents these 16 haplotypes ordered by their effect size for susceptibility to RA^[1] or for RA severity (presence of erosive disease^[2]). For severity, ORs are only given for high-frequency haplotypes, as the study by Viatte et al^[2] was underpowered to evaluate accurately effect sizes of low-frequency haplotypes. Haplotype names are given based on amino acids at positions 11, 71, and 74 (one-letter amino acid codes). Shared epitope alleles correspond to the VKA-, VRA-, and LRA-haplotypes. The column "Classical HLA-DRB1 alleles" shows only some examples of four-digit HLA types corresponding to the new classification.