Abstract
BackgroundTCF7L2 is a central transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway, and genetic variants in TCF7L2 have been found to interact with dietary fiber intake on type 2 diabetes risk. Here, we investigate whether other type 2 diabetes genes could be involved in the WNT signaling pathway and whether variants in such genes might interact with dietary fiber on type 2 diabetes incidence.ResultsWe included 26,905 individuals without diabetes from the Malmö Diet and Cancer Study cohort. Diet data was collected at baseline using a food frequency questionnaire, a 7-day food record, and an interview. Altogether, 51 gene loci were analyzed for putative links to WNT signaling. Over a mean follow-up period of 14.7 years, 3132 incident cases of type 2 diabetes were recorded. Seven genes (nine single nucleotide polymorphisms (SNPs)) were annotated as involved in WNT signaling including TCF7L2 (rs7903146 and rs12255372), HHEX (rs1111875), HNF1A (rs7957197), NOTCH2 (rs10923931), TLE4 (rs13292136), ZBED3 (rs4457053), and PPARG (rs1801282 and rs13081389). SNPs in TCF7L2, NOTCH2, and ZBED3 showed significant interactions with fiber intake on type 2 diabetes incidence (Pinteraction = 0.034, 0.005, 0.017, and 0.002, respectively). The magnitude of the association between the TCF7L2 risk allele and incident type 2 diabetes increased from the lowest to the highest quintiles of fiber intake. Higher fiber associated with lower type 2 diabetes risk only among risk allele carriers of the NOTCH2 variant and homozygotes of the risk allele of the ZBED3 variant.ConclusionsOur results suggest that several type 2 diabetes susceptibility SNPs in genes involved in WNT signaling may interact with dietary fiber intake on type 2 diabetes incidence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0524-4) contains supplementary material, which is available to authorized users.
Highlights
transcription factor 7like gene (TCF7L2) is a central transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway, and genetic variants in TCF7L2 have been found to interact with dietary fiber intake on type 2 diabetes risk
A total of 3132 incident cases of type 2 diabetes were recorded after a mean follow-up time of 14.7 years
Of the WNT-annotated single nucleotide polymorphism (SNP), we found, in addition to TCF7L2, the SNPs in NOTCH2 and ZBED3 loci (Table 4) to significantly interact with fiber intake on type 2 diabetes incidence
Summary
TCF7L2 is a central transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway, and genetic variants in TCF7L2 have been found to interact with dietary fiber intake on type 2 diabetes risk. TCF7L2 is a principal transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway [29]. This highlights the importance of the canonical WNT pathway in the pathogenesis of type 2 diabetes. Glucagon-like peptide-1 (GLP-1)-mediated proliferation of rat beta cell line (INS-1) has been shown to occur through activation of the WNT pathway [19]. Hindy et al Genes & Nutrition (2016) 11:6 activation of the WNT pathway has been observed to prevent pre-adipocyte differentiation [32]
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