1. ¹Complex Genetics Section, Department of Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands
2. ²Pediatric Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands
3. ³Department of Gastroenterology, VU University Medical Centre, Amsterdam, The Netherlands

Correspondence: Dr C Wijmenga, Complex Genetics Section, Department of Biomedical Genetics, Stratenum 2.117, University Medical Centre Utrecht, PO Box 85060, 3508 AB Utrecht, The Netherlands. Tel: +31 30 253 8427; Fax: +31 30 253 8479; E-mail: t.n.wijmenga@med.uu.nl

⁴These two authors contributed equally to this work.

Received 9 November 2005; Revised 11 April 2006; Accepted 25 April 2006; Published online 14 June 2006.

Abstract

Coeliac disease (CD) is a complex genetic disorder. Its etiology is owing to multiple genes and environmental factors, such as gluten. The first event in the pathogenesis of CD after the ingestion of gluten is the activation of a Th1 immune response that leads to villous atrophy. Although this immune response seems crucial to the disease's development, only the HLA-DQ2/DQ8 genes have been identified as causative immune genes related to CD. Recently, the activation of the transcription factor STAT1 and changes in its expression levels have confirmed the participation of the Janus kinase-signal transducer and activator of transcription pathway in CD. Furthermore, as the STAT-1 gene is a positional candidate located in the CELIAC3 locus on chromosome 2, we speculate that alterations in this gene could be primarily responsible for the aberrant immune response that characterizes CD. Based on this functional and genetic evidence, we investigated the primary contribution of STAT-1 to CD. We performed a comprehensive genetic association study using five tag SNPs fully covering the STAT-1 gene in a Dutch cohort of 355 independent CD cases and 360 healthy controls. Neither the alleles, nor the genotypes in the case–control genetic association studies, nor the haplotype analysis showed any association to the STAT-1 gene in the Dutch CD population. Our results do not point to a primary involvement of the STAT-1 gene in the Dutch CD population.