Genes involved in muscle contractility and nutrient signaling pathways within celiac disease risk loci show differential mRNA expression

BMC Medical Genetics

Åsa Torinsson Naluai¹  Daniel Agardh⁶  Staffan Nilsson⁴  Henrik Arnell⁵  Lars Browaldh³  Audur H. Gudjonsdottir²  Caroline Montén⁶ 

[1] Department of Medical & Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg, Sweden;Department of Pediatrics, Queen Silvia Children’s Hospital, Sahlgrenska Academy, Gothenburg, Sweden;Department of Clinical Science & Education, Karolinska Institute Södersjukhuset, Stockholm, Sweden;Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden;Department of Pediatric Gastroenterology, Hepatology & Nutrition, Karolinska University Hospital, Stockholm, Sweden;Diabetes & Celiac Disease Unit, Department of Clinical Sciences, Lund University, Jan Waldenströms gata 35, CRC, 91:10, Malmö, 202 05, Sweden

关键词: Single nucleotide polymorphisms;    Peripheral blood;    Small intestinal mucosa;    Gene expression;    Celiac Disease;   

Others  :  1220336
DOI  :  10.1186/s12881-015-0190-1

 received in 2014-10-20, accepted in 2015-06-16,  发布年份 2015

【 摘 要 】

Background

Risk gene variants for celiac disease, identified in genome-wide linkage and association studies, might influence molecular pathways important for disease development. The aim was to examine expression levels of potential risk genes close to these variants in the small intestine and peripheral blood and also to test if the non-coding variants affect nearby gene expression levels in children with celiac disease.

Methods

Intestinal biopsy and peripheral blood RNA was isolated from 167 children with celiac disease, 61 with potential celiac disease and 174 disease controls. Transcript levels for 88 target genes, selected from celiac disease risk loci, were analyzed in biopsies of a smaller sample subset by qPCR. Differentially expressed genes (3 from the pilot and 8 previously identified) were further validated in the larger sample collection (n = 402) of both tissues and correlated to nearby celiac disease risk variants.

Results

All genes were significantly down- or up-regulated in the intestinal mucosa of celiac disease children, NTS being most down-regulated (Fold change 3.6, p < 0.001). In contrast, PPP1R12B isoform C was up-regulated in the celiac disease mucosa (Fold change 1.9, p < 0.001). Allele specific expression of GLS (rs6741418, p = 0.009), INSR (rs7254060, p = 0.003) and NCALD (rs652008, p = 0.005) was also detected in the biopsies. Two genes (APPL2 and NCALD) were differentially expressed in peripheral blood but no allele specific expression was observed in this tissue.

Conclusion

The differential expression of NTS and PPP1R12B indicate a potential role for smooth muscle contractility and cell proliferation in celiac disease, whereas other genes like GLS, NCALD and INSR suggests involvement of nutrient signaling and energy homeostasis in celiac disease pathogenesis. A disturbance in any of these pathways might contribute to development of childhood celiac disease.

【 授权许可】

   
2015 Montén et al.

【 图 表 】

Fig. 1.

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