title: Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes.
abstract: BACKGROUND
  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. 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.
  
  
  RESULTS
  We 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 (P interaction = 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Clinical Sciences in Malmö, Lund University, Skåne University Hospital, Jan Waldenströms gata 35, SE-205 02 Malmö, Sweden.
authors.forename: George
authors.identifier: 0000-0002-7257-9299
authors.initials: G
authors.lastname: Hindy
authors.affiliation: Department of Clinical Sciences in Malmö, Lund University, Skåne University Hospital, Jan Waldenströms gata 35, SE-205 02 Malmö, Sweden.
authors.forename: Inês G
authors.initials: IG
authors.lastname: Mollet
authors.affiliation: Department of Clinical Sciences in Malmö, Lund University, Skåne University Hospital, Jan Waldenströms gata 35, SE-205 02 Malmö, Sweden.
authors.forename: Gull
authors.initials: G
authors.lastname: Rukh
authors.affiliation: Department of Clinical Sciences in Malmö, Lund University, Skåne University Hospital, Jan Waldenströms gata 35, SE-205 02 Malmö, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Ericson
authors.affiliation: Department of Clinical Sciences in Malmö, Lund University, Skåne University Hospital, Jan Waldenströms gata 35, SE-205 02 Malmö, Sweden.
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
keywords: Dietary fiber; Gene-diet interactions; TCF7L2; Type 2 diabetes; WNT signaling