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A diabetes-associated genetic variant is associated with diastolic dysfunction and cardiovascular disease

Molvin, John LU ; Jujic, Amra LU ; Nilsson, Peter M LU ; Leosdottir, Margret LU ; Lindblad, Ulf LU ; Daka, Bledar ; Bennet, Louise LU orcid ; Råstam, Lennart LU ; Lyssenko, Valeriya LU and Magnusson, Martin LU orcid (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
; ; ; ; ; ; ; ; and
organization
publishing date
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 &gt;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}},
}