Chromosomal region 16p13: further evidence of increased predisposition to immune diseases

A Martínez ¹, N Perdigones ¹, Mª Cénit ¹, L Espino ¹, J Varadé ¹, J R Lamas ¹, J L Santiago ¹, M Fernández-Arquero ¹, H de la Calle ², R Arroyo ¹, E G de la Concha ¹, B Fernandez-Gutierrez ¹ and E Urcelay ^1*

¹ Hospital Clínico San Carlos, Spain
² Hospital Ramón y Cajal, Spain

^* To whom correspondence should be addressed. E-mail: eurcelay.hcsc{at}salud.madrid.org.

Accepted 6 February 2009

Abstract

Objective: Genome-wide studies identified the chromosomal region 16p13 in type 1 diabetes (T1D) and multiple sclerosis (MS) susceptibility. This region includes the CLEC16A/KIAA0350 gene and an adjacent gene, MHC2TA (MHC class II transactivator), previously associated with MS and rheumatoid arthritis (RA) susceptibility. We tested the role of CLEC16A polymorphisms in T1D, MS and RA pathogenesis and its relationship with the association reported with a MHC2TA haplotype.

Methods: CLEC16A (rs2903692/rs6498169/rs11074956) polymorphisms were analyzed in 435 MS, 316 T1D and 600 RA patients and in 550 ethnically matched controls. The MHC2TA rs3087456G/rs4774C risk haplotype was studied in an independent RA cohort.

Results: rs2903692 conferred a protective effect to T1D, MS and RA patients. The described association of rs6498169 with MS was replicated in MS and in RA cohorts. We validated the effect of the MHC2TA rs3087456G/rs4774C haplotype on RA susceptibility and found the haplotype in negative linkage disequilibrium with the CLEC16A rs2903692A/rs6498169A haplotype.

Conclusion: Associations of CLEC16A polymorphisms with T1D and MS were successfully replicated in our Spanish population. We described the novel association of rs6498169 with RA predisposition, consistent with previous MHC2TA results. Our data evidence the influence of variants within this chromosomal region on the development of complex diseases.