A diabetes-associated genetic variant is associated with diastolic dysfunction and cardiovascular disease.
ESC Heart Fail
; 7(1): 348-356, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31860786
ABSTRACT
AIMS:
Although the epidemiological association between Type 2 diabetes and congestive heart failure (CHF) as well as cardiovascular disease (CVD) is well established, associations between diabetes-related single-nucleotide polymorphisms (SNPs), CHF, and CVD have been surprisingly inconclusive. Our aim is to examine if 43 diabetes-related SNPs were associated with prevalent diastolic dysfunction assessed by echocardiography and incident CVD and/or CHF. METHODS ANDRESULTS:
We genotyped 43 SNPs that previously reported genome-wide significant associations with Type 2 diabetes, in 1444 subjects from the population-based Malmö Preventive Project-Re-examination Study (MPP-RES) (mean age 68 years; 29% women, 36% prevalent diabetes) (discovery cohort) and in 996 subjects from the VARA cohort (mean age 51 years, 52% women, 7% prevalent diabetes) (replication cohort). Multivariable logistic regression was assessed. Genetic variants that reached significant association with diastolic dysfunction in both cohorts were then analysed for association with incident CVD/CHF in a larger sample of the MPP-RES cohort (3,407 cases and 11,776 controls, median follow up >30 years) using Cox regression analysis. A common variant at the HNF1B [major allele (T) coded, also the risk allele for diabetes] was the only SNP associated with increased risk of prevalent diastolic dysfunction in both the discovery [MPP-RES; odds ratio (OR) 1.21, P = 0.024), and the replication cohort (VARA; OR 1.38, P = 0.042]. Cox regression analysis showed that carriers of the T-allele of rs757210 had an increased risk of future CVD (HR 1.05, P = 0.042). No significant association was seen for incident CHF.CONCLUSIONS:
The diabetes susceptibility locus HNF1B is associated with prevalent diastolic dysfunction in two independent Swedish cohorts as well as incident cardiovascular disease.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Función Ventricular Izquierda
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Disfunción Ventricular Izquierda
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Polimorfismo de Nucleótido Simple
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Diabetes Mellitus Tipo 2
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Factor Nuclear 1-beta del Hepatocito
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Ventrículos Cardíacos
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2020
Tipo del documento:
Article