title: The PPARγ2 P12A polymorphism is not associated with all-cause mortality in patients with type 2 diabetes mellitus.
abstract: The high mortality risk of patients with type 2 diabetes mellitus may well be explained by the several comorbidities and/or complications. Also the intrinsic genetic component predisposing to diabetes might have a role in shaping the risk of diabetes-related mortality. Among type 2 diabetes mellitus SNPs, rs1801282 is of particular interest because (i) it is harbored by peroxisome proliferator-activated receptor-γ2 (PPARγ2), which is the target for thiazolidinediones which are used as antidiabetic drugs, decreasing all-cause mortality in type 2 diabetes mellitus, and (ii) it is associated with insulin resistance and related traits, risk factors for overall mortality in type 2 diabetes mellitus. We investigated the role of PPARγ2 P12A, according to a dominant model (PA + AA vs. PP individuals) on incident all-cause mortality in three cohorts of type 2 diabetes mellitus, comprising a total of 1672 patients (462 deaths) and then performed a meta-analysis of ours and all available published data. In the three cohorts pooled and analyzed together, no association between PPARγ2 P12A and all-cause mortality was observed (HR 1.02, 95 % CI 0.79-1.33). Similar results were observed after adjusting for age, sex, smoking habits, and BMI (HR 1.09, 95 % CI 0.83-1.43). In a meta-analysis of ours and all studies previously published (n = 3241 individuals; 666 events), no association was observed between PPARγ2 P12A and all-cause mortality (HR 1.07, 95 % CI 0.85-1.33). Results from our individual samples as well as from our meta-analysis suggest that the PPARγ2 P12A does not significantly affect all-cause mortality in patients with type 2 diabetes mellitus.
authors.affiliation: Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pacilli
authors.affiliation: Mendel-Laboratory, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Prudente
authors.affiliation: Unit of Biostatistics, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Unit of Biostatistics, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Mendel-Laboratory, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Mercuri
authors.affiliation: Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bacci
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, Scientific Institute "Casa Sollievo della Sofferenza", Viale Padre Pio, 71013, San Giovanni Rotondo, FG, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Marucci
authors.affiliation: Mendel-Laboratory, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Alberico
authors.affiliation: Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Viti
authors.affiliation: Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palena
authors.affiliation: Unit of Endocrinology and Metabolic Diseases, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Lamacchia
authors.affiliation: Unit of Endocrinology and Metabolic Diseases, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cignarelli
authors.affiliation: Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.affiliation: Mendel-Laboratory, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy. vincenzo.trischitta@uniroma1.it.|Research Unit of Diabetes and Endocrine Diseases, Scientific Institute "Casa Sollievo della Sofferenza", Viale Padre Pio, 71013, San Giovanni Rotondo, FG, Italy. vincenzo.trischitta@uniroma1.it.|Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy. vincenzo.trischitta@uniroma1.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000401:mortality; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D047495:PPAR gamma
keywords: Overall mortality; PPARγ2 P12A SNP; Risk of death; Type 2 diabetes