Evidence that glioma-associated oncogene homolog 1 is not a universal risk gene for inflammatory bowel disease in Caucasians

Abstract

The transcription factor glioma-associated oncogene homolog 1 (GLI1) has a central function in gastrointestinal tract development and homeostasis. A non-synonymous single-nucleotide polymorphism (SNP) (rs2228226; Q1100E) in GLI1, which impairs GLI1 function in vitro, has been proposed as a risk factor for inflammatory bowel disease (IBD). In this study, we assessed the cumulative evidence for association of GLI1 with IBD. New genotype data for rs2228226 from New Zealand (907 controls, 990 IBD patients) and Belgian Caucasian case-control data sets (312 controls, 1214 IBD patients) were combined with data from the National Institute of Diabetes and Digestive and Kidney Diseases and three previously studied Caucasian case-control data sets. Meta-analysis of rs2228226 did not detect any association with ulcerative colitis (UC) (P ¼ 0.09, odds ratio (OR) ¼ 1.07, 95% confidence interval (CI) ¼ 0.92-1.24), Crohn's disease (CD) (P ¼ 0.29, OR ¼ 1.06, 95% CI ¼ 0.93-1.21) or overall IBD (P ¼ 0.15, OR ¼ 1.05, 95% CI ¼ 0.92-1.19). Our analyses of rs2228226 suggest that GLI1 is not a significant risk factor for IBD in Caucasians.

Vitamin D receptor gene polymorphism associated with inflammatory bowel disease in New Zealand males

“…The aim of this study was to replicate and expand on the findings of Noble et al. 1 by investigating the association of three SNPs of the VDR gene, rs11568820, rs2228570 and rs731236 , in a well‐phenotyped, Caucasian IBD cohort 4, 5 . All participants gave informed consent and ethical approval for the study was obtained.…”

Major signaling pathways in intestinal stem cells

“…Bentley and colleagues showed that the identified GLI1 SNP does not increase susceptibility to IBD across all the Caucasian populations, but it also does not exclude a contribution to UC onset in the populations studied by Lees et al . [162]. …”