Genome-wide studies have identified the chromosomal region 16p13 in the susceptibility to type 1 diabetes (T1D) and multiple sclerosis (MS). This region includes the CLEC16A/KIAA0350 gene and an adjacent gene, MHC2TA (MHC class II transactivator), previously associated with susceptibility to MS and rheumatoid arthritis (RA). The role of CLEC16A polymorphisms in the pathogenesis of T1D, MS and RA and its relationship with the association reported with a MHC2TA haplotype were investigated.
CLEC16A (rs2903692/rs6498169/rs11074956) polymorphisms were analysed in 435 patients with MS, 316 with T1D and 600 with RA and in 550 ethnically matched controls. The MHC2TA rs3087456G/rs4774C risk haplotype was studied in an independent RA cohort.
rs2903692 conferred a protective effect on patients with T1D, MS and RA. The described association of rs6498169 with MS was replicated in MS and RA cohorts. The effect of the MHC2TA rs3087456G/rs4774C haplotype on RA susceptibility was confirmed, and the haplotype was found to be in negative linkage disequilibrium with the CLEC16A rs2903692A/rs6498169A haplotype.
Associations of CLEC16A polymorphisms with T1D and MS were successfully replicated in a Spanish population. A novel association of rs6498169 with a predisposition to RA was described which is consistent with previous MHC2TA results. These data provide evidence for the influence of variants within this chromosomal region on the development of complex diseases.