Autoimmune disease association signals in CIITA and KIAA0350 are not involved in celiac disease susceptibility

Abstract

Celiac disease (CD) is a multifactorial disease characterized by intestinal inflammation after gluten exposure in genetically susceptible individuals. A strong influence of certain human leukocyte antigen (HLA) alleles (those coding the HLA-DQ2 and DQ8 heterodimers) is well established, but they cannot explain the overall genetic risk. CIITA could be a good candidate gene for CD because it is mainly transcriptionally regulated, and it encodes the master regulator of major histocompatibilty complex class II gene transcription. CIITA is located in 16p13, a region also containing KIAA0350 (CLEC16A), associated with two autoimmune diseases in genome-wide association studies. We aimed at studying the involvement of polymorphisms in CIITA and KIAA0350 in CD susceptibility, with special attention to evaluate the possible presence of more than one risk factor in the region. We performed a case-control study with 607 CD patients and up to 794 healthy controls, all Spaniards. All samples were genotyped for five single nucleotide polymorphisms: rs3087456 (-168A/G) and rs4774 in CIITA and rs7203459, rs6498169 and rs2903692 in KIAA0350. No significant results were obtained when comparing genotypic, allelic or haplotypic frequencies between patients and controls. Our results seem to discard the influence in CD susceptibility of CIITA and KIAA0350 markers previously associated with other autoimmune diseases.