Joint effect of insulin signaling genes on all-cause mortality
| Autor: | Simonetta Bacci, Timothy Hastings, Antonella Marucci, Massimiliano Copetti, Stefano Rizza, Francesca Mallamaci, Salvatore De Cosmo, Christine Mendonca, Belinda Spoto, Vincenzo Trischitta, Alessandro Doria, Massimo Federici, Alessandra Testa, Andrea Fontana, Carmine Zoccali, Giovanni Tripepi, Claudia Menzaghi, Diego Bailetti, Patinut Buranasupkajorn |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Oncology medicine.medical_specialty Settore MED/09 - Medicina Interna Genotype medicine.medical_treatment Myocardial Infarction Single-nucleotide polymorphism Type 2 diabetes Polymorphism Single Nucleotide Article Insulin resistance Internal medicine medicine Humans Insulin Genetic Predisposition to Disease Prospective Studies Settore MED/49 - Scienze Tecniche Dietetiche Applicate Mortality Alleles Aged Proportional Hazards Models Genetics ENPP1 IRS1 TRIB3 Prospective study Proportional hazards model business.industry Mortality rate Confounding Genetic Variation Middle Aged Atherosclerosis medicine.disease Treatment Outcome Diabetes Mellitus Type 2 Italy Cardiovascular Diseases Female Insulin Resistance Cardiology and Cardiovascular Medicine business Signal Transduction |
| Zdroj: | Atherosclerosis. 237:639-644 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2014.10.005 |
| Popis: | Objective : We have previously reported the combined effect of SNPs perturbing insulin signaling ( ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular events. We here investigated whether such a combined effect affects also all-cause mortality in a sample of 1851 Whites of European ancestry. Methods : We investigated a first sample of 721 patients, 232 deaths, 3389 person-years (py). Replication was assessed in two samples of patients with T2D: the Gargano Mortality Study (GMS) of 714 patients, 127 deaths, 5426 py and the Joslin Kidney Study (JKS) comprising 416 patients, 214 deaths, 5325 py. Results : In the first sample, individuals carrying 1 or ≥2 risk alleles had 33% ( p = 0.06) and 51% ( p = 0.02) increased risk of mortality, as compared with individuals with no risk alleles. A similar, though not significant, trend was obtained in the two replication samples only for subject carrying ≥ 2 risk alleles. In a pooled analysis, individuals carrying ≥2 risk alleles had higher mortality rate as compared to those carrying 0 risk alleles (HR = 1.34, 95%CI = 1.08–1.67; p = 0.008), and as compared to those carrying only one risk allele (HR = 1.41, 95%CI = 1.13–1.75; p = 0.002). This association was independent from several possible confounders including sex, age, BMI, hypertension and diabetes status. Conclusion : Our data suggest that variants affecting insulin signaling exert a joint effect on all-cause mortality and is consistent with a role of abnormal insulin signaling on mortality risk. |
| Databáze: | OpenAIRE |
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