A diabetes-associated genetic variant is associated with diastolic dysfunction and cardiovascular disease
(2020) In ESC Heart Failure 7(1). p.345-353- 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 AND RESULTS: 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)... (More)
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 AND RESULTS: 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.
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- author
- Molvin, John LU ; Jujic, Amra LU ; Nilsson, Peter M LU ; Leosdottir, Margret LU ; Lindblad, Ulf LU ; Daka, Bledar ; Bennet, Louise LU ; Råstam, Lennart LU ; Lyssenko, Valeriya LU and Magnusson, Martin LU
- organization
-
- Cardiovascular Research - Hypertension (research group)
- Internal Medicine - Epidemiology (research group)
- EpiHealth: Epidemiology for Health
- EXODIAB: Excellence of Diabetes Research in Sweden
- Family Medicine and Community Medicine (research group)
- Genomics, Diabetes and Endocrinology (research group)
- WCMM-Wallenberg Centre for Molecular Medicine
- publishing date
- 2020-02
- type
- Contribution to journal
- publication status
- published
- subject
- in
- ESC Heart Failure
- volume
- 7
- issue
- 1
- pages
- 9 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85076894311
- pmid:31860786
- ISSN
- 2055-5822
- DOI
- 10.1002/ehf2.12573
- project
- Nationwide research collaboration in family medicine and type 2 diabetes - Swedish Primary Care Diabetes (SPACE)
- language
- English
- LU publication?
- yes
- additional info
- © 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
- id
- 808e81f6-003e-4350-a72d-b12eeaaf23d1
- date added to LUP
- 2019-12-27 13:58:27
- date last changed
- 2024-01-31 13:57:01
@article{808e81f6-003e-4350-a72d-b12eeaaf23d1, abstract = {{<p>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.</p><p>METHODS AND RESULTS: 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.</p><p>CONCLUSIONS: The diabetes susceptibility locus HNF1B is associated with prevalent diastolic dysfunction in two independent Swedish cohorts as well as incident cardiovascular disease.</p>}}, author = {{Molvin, John and Jujic, Amra and Nilsson, Peter M and Leosdottir, Margret and Lindblad, Ulf and Daka, Bledar and Bennet, Louise and Råstam, Lennart and Lyssenko, Valeriya and Magnusson, Martin}}, issn = {{2055-5822}}, language = {{eng}}, number = {{1}}, pages = {{345--353}}, publisher = {{John Wiley & Sons Inc.}}, series = {{ESC Heart Failure}}, title = {{A diabetes-associated genetic variant is associated with diastolic dysfunction and cardiovascular disease}}, url = {{http://dx.doi.org/10.1002/ehf2.12573}}, doi = {{10.1002/ehf2.12573}}, volume = {{7}}, year = {{2020}}, }