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Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes.
- Source :
-
Scientific reports [Sci Rep] 2019 Jul 17; Vol. 9 (1), pp. 10395. Date of Electronic Publication: 2019 Jul 17. - Publication Year :
- 2019
-
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.
- Subjects :
- Aged
Cohort Studies
Diabetes Mellitus, Type 2 complications
Female
Genetic Predisposition to Disease genetics
Haplotypes genetics
Humans
Italy
Linkage Disequilibrium genetics
Male
Middle Aged
Polymorphism, Single Nucleotide genetics
Proportional Hazards Models
Risk Factors
Diabetes Mellitus, Type 2 genetics
Diabetes Mellitus, Type 2 mortality
Erythropoietin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 31316151
- Full Text :
- https://doi.org/10.1038/s41598-019-46894-2