title: IRS1 G972R missense polymorphism is associated with failure to oral antidiabetes drugs in white patients with type 2 diabetes from Italy.
abstract: This study tried to replicate in a large sample of white patients with type 2 diabetes (T2D) from Italy a previously reported association of the IRS1 G972R polymorphism with failure to oral antidiabetes drugs (OAD). A total of 2,409 patients from four independent studies were investigated. Case subjects (n = 1,193) were patients in whom, because of uncontrolled diabetes (i.e., HbA1c >8%), insulin therapy had been added either on, or instead of, maximal or near-maximal doses of OAD, mostly metformin and sulfonylureas; control subjects (n = 1,216) were patients with HbA1c <8% in the absence of insulin therapy. The IRS1 G972R polymorphism was typed by TaqMan allele discrimination. In all samples, individuals carrying the IRS1 R972 risk variant tended to be more frequent among case than control subjects, though reaching statistical significance only in one case. As no IRS1 G972R-by-study sample interaction was observed, data from the four samples were analyzed together; a significant association was observed (allelic odds ratio [OR] 1.30, 95% CI 1.03-1.63). When our present data were meta-analyzed with those obtained in a previous study, an overall R972 allelic OR of 1.37 (1.12-1.69) was observed. This study confirms in a large and ethnically homogeneous sample that IRS1 G972R polymorphism is associated with failure to OAD among patients with T2D.
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy s.prudente@css-mendel.it vincenzo.trischitta@uniroma1.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Prudente
authors.affiliation: Department of Experimental Medicine, Sapienza University, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Morini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lucchesi
authors.affiliation: Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Lamacchia
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy Department of Experimental Medicine, Sapienza University, Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Bailetti
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Mercuri
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Alberico
authors.affiliation: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Institute of Agricultural Biology and Biotechnology, CNR, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pucci
authors.affiliation: Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Fariello
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Giusti
authors.affiliation: Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cignarelli
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Penno
authors.affiliation: Clinical Unit of Endocrinology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy Department of Experimental Medicine, Sapienza University, Rome, Italy Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy s.prudente@css-mendel.it vincenzo.trischitta@uniroma1.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007558:Italy; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D020125:Mutation, Missense; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D044465:White People / Q000235:genetics
chemical_list: D007004:Hypoglycemic Agents; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D013453:Sulfonylurea Compounds; D008687:Metformin