BACKGROUND: Transgenic mice over-expressing SMAD7 in pancreatic beta-cells develop type 2 diabetes (T2D). The expression of SMAD7 is affected by KLF11, which contains gene variants that have previously been shown to be involved in genetic susceptibility to T2D, and by the highly homologous KLF10. This study aims to assess the genetic contribution of SMAD7 and KLF10 gene variants to T2D susceptibility in the French population. METHODS: We screened both genes to identify rare and frequent variants by direct sequencing and then genotyped these variants. Six frequent variants of SMAD7 and six of KLF10 were analyzed in 349 T2D patients and 349 normoglycaemic adult subjects. Variants with statistically significant differences in allele and/or genotype distribution were further analyzed in a population sample of 1.712 T2D patients and 1.072 normoglycaemic subjects. RESULTS: Two variants showed a significant association under a recessive model: The intronic SMAD7 IVS2 -21 had an odds ratio of 0.62 (P=0.007, 95% CI=0.44-0.88; P=0.034 when adjusting for age, sex and BMI by logistic regression), and the KLF10 3'UTR +1002 variant had an Odds Ratio of 0.81 (P=0.009, 95% CI=0.69-0.95; P=0.042 when adjusting for age, sex and BMI). CONCLUSION: Although the observed association of SMAD7 and KLF10 gene variants with T2D is modest, they may weakly contribute to a particular genetic background that increases the susceptibility to development of T2D.
BACKGROUND:Transgenic mice over-expressing SMAD7 in pancreatic beta-cells develop type 2 diabetes (T2D). The expression of SMAD7 is affected by KLF11, which contains gene variants that have previously been shown to be involved in genetic susceptibility to T2D, and by the highly homologous KLF10. This study aims to assess the genetic contribution of SMAD7 and KLF10 gene variants to T2D susceptibility in the French population. METHODS: We screened both genes to identify rare and frequent variants by direct sequencing and then genotyped these variants. Six frequent variants of SMAD7 and six of KLF10 were analyzed in 349 T2D patients and 349 normoglycaemic adult subjects. Variants with statistically significant differences in allele and/or genotype distribution were further analyzed in a population sample of 1.712 T2D patients and 1.072 normoglycaemic subjects. RESULTS: Two variants showed a significant association under a recessive model: The intronic SMAD7 IVS2 -21 had an odds ratio of 0.62 (P=0.007, 95% CI=0.44-0.88; P=0.034 when adjusting for age, sex and BMI by logistic regression), and the KLF10 3'UTR +1002 variant had an Odds Ratio of 0.81 (P=0.009, 95% CI=0.69-0.95; P=0.042 when adjusting for age, sex and BMI). CONCLUSION: Although the observed association of SMAD7 and KLF10 gene variants with T2D is modest, they may weakly contribute to a particular genetic background that increases the susceptibility to development of T2D.
Authors: Konstantinos A Papadakis; James Krempski; Phyllis Svingen; Yuning Xiong; Olga F Sarmento; Gwen A Lomberk; Raul A Urrutia; William A Faubion Journal: Am J Physiol Gastrointest Liver Physiol Date: 2015-10-15 Impact factor: 4.052
Authors: Malayannan Subramaniam; John R Hawse; Nalini M Rajamannan; James N Ingle; Thomas C Spelsberg Journal: Biofactors Date: 2010 Jan-Feb Impact factor: 6.113
Authors: Xuejuan Jiang; J Esteban Castelao; David Vandenberg; Angel Carracedo; Carmen M Redondo; David V Conti; Jesus P Paredes Cotoré; John D Potter; Polly A Newcomb; Michael N Passarelli; Mark A Jenkins; John L Hopper; Steven Gallinger; Loic Le Marchand; María E Martínez; Dennis J Ahnen; John A Baron; Noralane M Lindor; Robert W Haile; Manuela Gago-Dominguez Journal: PLoS One Date: 2013-04-03 Impact factor: 3.240