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A diabetes associated HNF1B polymorphism increases risk of prevalent diastolic dysfunction in two independent Swedish population cohorts

Session Diastolic function

Speaker John Molvin

Event : ESC Congress 2016

  • Topic : heart failure
  • Sub-topic : Diastolic Ventricular Dysfunction
  • Session type : Moderated Posters

Authors : J Molvin (Lund,SE), PM Nilsson (Malmö,SE), M Leosdottir (Lund,SE), U Lindblad (Gothenburg,SE), B Daka (Gothenburg,SE), L Bennet (Malmö,SE), L Rastam (Malmö,SE), O Melander (Malmö,SE), V Lyssenko (Lund,SE), M Magnusson (Lund,SE)

J. Molvin1 , P.M. Nilsson2 , M. Leosdottir1 , U. Lindblad3 , B. Daka3 , L. Bennet2 , L. Rastam2 , O. Melander2 , V. Lyssenko4 , M. Magnusson1 , 1Skane University Hospital, Department of Cardiology, Skåne University Hospital Malmö - Lund - Sweden , 2Department of Clinical Sciences, Lund University, Skåne University Hospital - Malmö - Sweden , 3University of Gothenburg, Institute of Medicine, Department of Public Health and Community Medicine, Sahlgrenska Academy - Gothenburg - Sweden , 4Lund University, Department of Clinical Sciences, Diabetes and Endocrinology, Diabetes Center, Malmö Sweden. - Lund - Sweden ,

On behalf: HARVEST - HeARt and brain failure inVESTigation study group

European Heart Journal ( 2016 ) 37 ( Abstract Supplement ), 814

Background: Although diabetes, hyperglycemia and insulin resistance increase risk of future cardiovascular disease (CVD), earlier genetic studies have failed to show associations between diabetes-related single-nucleotide polymorphisms (SNPs) and CVD-risk.

Purpose: To examine if 43 SNPs with earlier established genome wide association with increased risk of type 2 diabetes (T2D), hyperglycemia and insulin resistance were also associated with prevalent early signs of diastolic dysfunction (DD) as measured by echocardiographical examination (UCG) in two independent Swedish population-based cohorts.

Methods: We genotyped 43 SNPs in 43 genes that reported genome-wide significant association with T2D, hyperglycemia and insulin resistance traits, in 1792 subjects from the population-based Malmö Preventive Project (MPP) with full UCG data (mean age 68 years; 29% women, 36% prevalent T2D) (discovery cohort) and in 996 subjects from the VARA cohort with full UCG data (mean age 51 years, 52% women, 7% prevalent T2D) (replication cohort). Logistic regression was used to adjust for covariates (age, sex, systolic and diastolic blood pressure, hypertensive treatment and diabetes status).

Results: In the fully adjusted logistic regression analysis of the MPP cohort common variants in 4 genes were significantly associated (p<0.05) with increased risk of prevalent DD: ADAMTS9 (Odds ratio (OR), 1.22, p=0.045), HNF1B (OR, 1.21, p=0.028), JAZF1 (OR, 1.18, p=0.044), TSPAN8 (OR, 1.25, p=0.023) and common variants in 4 genes were associated with decreased risk of prevalent DD: HNF1A (OR, 0.77; p=0.011), KLF14 (OR, 0.85, p=0.044), TCF7L2 (OR, 0.81, p=0.018), NOTCH2 (OR, 0.72, p=0.021). When these 8 SNPs were tested in the replication cohort only one SNP reached nominal significant association with DD in the fully adjusted logistic regression analysis; HNF1B rs757210 (OR, 1.38, p=0.042).

Conclusion: Here we show that an identified in GWAS T2D susceptibility locus HNF1B is also associated with increased risk of prevalent DD as measured by UCG in two independent Swedish cohorts.

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