Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetesReportar como inadecuado




Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Genes and Nutrition

, 11:6

First Online: 21 March 2016Received: 22 October 2015Accepted: 07 March 2016DOI: 10.1186-s12263-016-0524-4

Cite this article as: Hindy, G., Mollet, I.G., Rukh, G. et al. Genes Nutr 2016 11: 6. doi:10.1186-s12263-016-0524-4

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.

KeywordsGene-diet interactions TCF7L2 WNT signaling Type 2 diabetes Dietary fiber AbbreviationsCIconfidence interval

FFAR2free fatty acid receptor 2

FPGfasting plasma glucose

FPIfasting plasma insulin

GLP-1glucagon-like peptide-1

GWASgenome-wide association study

HbA1Cglycated hemoglobin

HOMA-IRhomeostasis model for assessment of insulin resistance

HRhazard ratio

MDC-CCMalmö Diet and Cancer Study Cardiovascular Cohort

MDCSMalmö Diet and Cancer Study

SCFAshort chain fatty acid

SNPsingle nucleotide polymorphism

TCF7L2transcription factor 7-like 2 gene

WNTwingless-type MMTV integration site

Electronic supplementary materialThe online version of this article doi:10.1186-s12263-016-0524-4 contains supplementary material, which is available to authorized users.

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Autor: George Hindy - Inês G. Mollet - Gull Rukh - Ulrika Ericson - Marju Orho-Melander

Fuente: https://link.springer.com/







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