title: The osteopontin gene +1239A/C single nucleotide polymorphism is associated with type 1 diabetes mellitus in the Italian population.
abstract: Secreted phosphoprotein 1, also known as Osteopontin (Opn), is a proinflammatory cytokine involved in the TH1 response and is highly expressed in the islets and pancreatic lymph nodes of non-obese diabetic mice before the onset of diabetes. In humans, typing of the +1239A/C single nucleotide polymorphism (SNP) in the 3UTR of the Opn gene (SPP1) showed that +1239C carriers displayed higher Opn serum levels than +1239A homozygotes and a higher risk of developing autoimmune/lymphoproliferative syndrome, multiple sclerosis, and systemic lupus erythematosus. The aim of this work is to evaluate whether +1239A/C is also associated with type 1 diabetes mellitus (T1DM). We typed +1239A/C in an initial cohort of 184 T1DM patients and 361 controls, and confirmed our data in a second cohort of 513 patients and 857 controls. In both cohorts, +1239C carriers displayed a significantly higher risk of T1DM than +1239A homozygotes (combined cohorts: OR=1.63, 95 percent CI: 1.34-1.97). Clinical analysis did not detect any differences between patients carrying or not +1239C in terms of gender distribution and age at T1DM diagnosis. These data suggest that SPP1 variants marked by +1239C are associated with T1DM development in the Italian population. The predisposing effect may depend on its effect on Opn levels.
authors.affiliation: Interdisciplinary Research Center of Autoimmune Diseases and Department of Medical Sciences, A. Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: E
authors.initials: E
authors.lastname: Orilieri
authors.forename: G
authors.initials: G
authors.lastname: Cappellano
authors.forename: N
authors.initials: N
authors.lastname: Barizzone
authors.forename: S
authors.initials: S
authors.lastname: D' Alfonso
authors.forename: G
authors.initials: G
authors.lastname: D' Annunzio
authors.forename: R
authors.initials: R
authors.lastname: Lorini
authors.forename: R
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: F
authors.initials: F
authors.lastname: Cadario
authors.forename: M
authors.initials: M
authors.lastname: Martinetti
authors.forename: V
authors.initials: V
authors.lastname: Calcaterra
authors.forename: F
authors.initials: F
authors.lastname: Cerutti
authors.forename: G
authors.initials: G
authors.lastname: Bruno
authors.forename: D
authors.initials: D
authors.lastname: Larizza
authors.forename: U
authors.initials: U
authors.lastname: Dianzani
mesh_terms: D000293:Adolescent; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D008297:Male; D053495:Osteopontin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055503:Protein Multimerization
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; C506895:SPP1 protein, human; D053495:Osteopontin