title: No association between variation of the FOXP3 gene and common type 1 diabetes in the Sardinian population.
abstract: Mutations of the forkhead/winged helix transcription factor FOXP3 gene on chromosome Xp11.23 cause a rare recessive monogenic disorder called IPEX (immune dysregulation, polyendocrinopathy, including type 1 diabetes, enteropathy, and X-linked syndrome). FOXP3 is necessary for the differentiation of a key immune suppressive subset of T-cells, the CD4+CD25+ regulatory T-cells. Previously, we reported a significant male-female bias in the common, multifactorial form of type 1 diabetes in Sardinia and evidence of linkage of chromosome Xp11 to the disease. These findings indicate that FOXP3 is a prime functional and positional candidate locus for the common form of type 1 diabetes. In the present study, we initially scanned 82 kb of the FOXP3 region for common polymorphisms, including sequencing all of the coding and functionally relevant portions of the gene in 64 Sardinian individuals. Then the most informative polymorphisms in 418 type 1 diabetic families and in 268 male case and 326 male control subjects were sequentially genotyped and tested for disease association. There is no evidence that variants in the FOXP3 regions analyzed are associated with type 1 diabetes and account for the male-female bias observed in Sardinia. Our data indicate that allelic variation in or near the coding regions of the FOXP3 gene does not have a major role in the inherited susceptibility to the common form of type 1 diabetes.
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Ospedale Microcitemico, Cagliari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zavattari
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Deidda
authors.forename: Maristella
authors.initials: M
authors.lastname: Pitzalis
authors.forename: Barbara
authors.initials: B
authors.lastname: Zoa
authors.forename: Loredana
authors.initials: L
authors.lastname: Moi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Lampis
authors.forename: Daniela
authors.initials: D
authors.lastname: Contu
authors.forename: Costantino
authors.initials: C
authors.lastname: Motzo
authors.forename: Paola
authors.initials: P
authors.lastname: Frongia
authors.forename: Efisio
authors.initials: E
authors.lastname: Angius
authors.forename: Mario
authors.initials: M
authors.lastname: Maioli
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucca
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D004268:DNA-Binding Proteins / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D051858:Forkhead Transcription Factors; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D011110:Polymorphism, Genetic
chemical_list: D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors