Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes

Alberto Montesano, Anna Rita Bonfigli, Maria De Luca, Paolina Crocco, Paolo Garagnani, Elena Marasco, Chiara Pirazzini, Cristina Giuliani, Fabio Romagnoli, Claudio Franceschi, Giuseppe Passarino, Roberto Testa, Fabiola Olivieri, Giuseppina Rose

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Abstract

Type-2 Diabetes (T2D), diabetic complications, and their clinical risk factors harbor a substantial genetic component but the genetic factors contributing to overall diabetes mortality remain unknown. Here, we examined the association between genetic variants at 21 T2D-susceptibility loci and all-cause mortality in an elderly cohort of 542 Italian diabetic patients who were followed for an average of 12.08 years. Univariate Cox regression analyses detected age, waist-to-hip ratio (WHR), glycosylated haemoglobin (HbA1c), diabetes duration, retinopathy, nephropathy, chronic kidney disease (CKD), and anaemia as predictors of all-cause mortality. When Cox proportional hazards multivariate models adjusted for these factors were run, three erythropoietin (EPO) genetic variants in linkage disequilibrium (LD) with each other (rs1617640-T/G, rs507392-T/C and rs551238-A/C) were significantly (False Discovery Rate < 0.1) associated with mortality. Haplotype multivariate analysis revealed that patients carrying the G-C-C haplotype have an increased probability of survival, while an opposite effect was observed among subjects carrying the T-T-A haplotype. Our findings provide evidence that the EPO gene is an independent predictor of mortality in patients with T2D. Thus, understanding the mechanisms by which the genetic variability of EPO affects the mortality of T2D patients may provide potential targets for therapeutic interventions to improve the survival of these patients.

Original languageEnglish
Article number10395
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Erythropoietin
Type 2 Diabetes Mellitus
Haplotypes
Mortality
Diabetes Complications
Waist-Hip Ratio
Survival
Linkage Disequilibrium
Glycosylated Hemoglobin A
Chronic Renal Insufficiency
Proportional Hazards Models
Anemia
Multivariate Analysis
Regression Analysis
Genes

ASJC Scopus subject areas

  • General

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Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes. / Montesano, Alberto; Bonfigli, Anna Rita; De Luca, Maria; Crocco, Paolina; Garagnani, Paolo; Marasco, Elena; Pirazzini, Chiara; Giuliani, Cristina; Romagnoli, Fabio; Franceschi, Claudio; Passarino, Giuseppe; Testa, Roberto; Olivieri, Fabiola; Rose, Giuseppina.

In: Scientific Reports, Vol. 9, No. 1, 10395, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Franceschi, Claudio

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