Expression analysis of celiac disease candidate genes in the 6q22 GWAs peak

BONDAR, CONSTANZA; PLAZA-IZURIETA, LETICIA; FERNANDEZ-JIMENEZ, NORA; IRASTORZA, IÑAKI; CEGEC; WIJMENGA, CISCA; CHIRDO, FERNANDO; VITORIA, JUAN CARLOS; BILBAO, JOSE RAMON

Conferencia; European Conference of Human Genetics 2012; 2012

European Society of Human Genetics

Coeliac disease (CD) is an immune mediated, multigenic disorder where HLA-DQ2/DQ8 contributes about 35% to genetic risk. GWAS have found more than 26 regions for CD susceptibility, and several potentially functional candidate genes have been located within. Recently, the IMMUNOCHIP genotyping array discovered additional 13 regions of susceptibility. The GWAS signal in chromosome 6:128.0-128.4 kb pointed to THEMIS and PTPRK as possible candidate genes, both with immune-related function. The signal was narrowed to the PTPRK region in the subsequent study, but functional confirmation is pending. The aim of this work was to determine the influence of associated SNPs on THEMIS and PTPRK gene expression in the intestinal mucosa of active and treated CD patients and controls. We assessed the correlation between qPCR expression levels and SNP genotypes of the top SNPs in both studies (rs802734, rs55743914 and rs72975916) and those most strongly associated in our CEGEC population (rs10484718 and rs9491896). THEMIS showed higher expression in active CD compared to treated patients and controls, while PTPRK showed lower expression. Our study confirmed an association of this region with CD in the local population, although only rs802734 genotype showed any influence in THEMIS expression. Interestingly we found a significant positive correlation between THEMIS and PTPRK mRNA levels in CD patients but not in controls. Our results suggest a possible role for both candidate genes in CD pathogenesis although further investigation is needed to clarify the impact of the associated SNPs on their expression.