title: Serum resistin is causally related to mortality risk in patients with type 2 diabetes: preliminary evidences from genetic data.
abstract: Resistin has been firmly associated with all-cause mortality. We investigated, whether, in patients with type 2 diabetes (T2D), this association is sustained by a cause-effect relationship. A genotype risk score (GRS), created by summing the number of resistin increasing alleles of two genome-wide association studies (GWAS)-derived single nucleotide polymorphisms (SNPs), serum resistin measurements and all-cause death records were obtained in 1,479 (403 events/12,454 person-years), patients with T2D from three cohorts, Gargano Heart Study-prospective design (n = 350), Gargano Mortality Study (n = 698) and Foggia Mortality Study (n = 431), from Italy. GRS was strongly associated with serum resistin in a non-linear fashion (overall p = 3.5 * 10-7) with effect size modest for GRS = 1 and 2 and much higher for GRS >3, with respect to GRS = 0. A significant non-linear association was observed also between GRS and all-cause mortality (overall p = 3.3 * 10-2), with a low effect size for GRS = 1 and 2, and nearly doubled for GRS ≥ 3, with respect to GRS = 0. Based on the above-reported associations, each genetic equivalent SD increase in log-resistin levels showed a causal hazard ratio of all-cause mortality equal to 2.17 (95%CI: 1.22-3.87), thus providing evidence for a causal role of resistin in shaping the risk of mortality in diabetic patients.
authors.affiliation: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Ortega Moreno
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: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: De Bonis
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Salvemini
authors.affiliation: Division of Internal Medicine, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
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: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 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
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. c.menzaghi@operapadrepio.it.
authors.forename: Claudia
authors.identifier: 0000-0002-7438-8955
authors.initials: C
authors.lastname: Menzaghi
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000401:mortality; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D052243:Resistin / Q000097:blood* / Q000235:genetics; D012306:Risk
chemical_list: D052243:Resistin