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Diabetes associated DNA variants relation with prevalent left ventricular hypertrophy and diastolic dysfunction

Session Poster Session 2

Speaker John Molvin

Event : Heart Failure 2016

  • Topic : basic science
  • Sub-topic : Basic Science - Cardiac Biology and Physiology
  • Session type : Poster Session

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

M Magnusson1 , J Molvin1 , PM Nilsson1 , M Leosdottir1 , U Lindblad2 , B Daka2 , L Bennet1 , L Rastam1 , O Melander1 , V Lyssenko1 , 1Department of Clinical Sciences, Lund University, Skåne University Hospital - Malmö - Sweden , 2University of Gothenburg, Institute of Medicine, Department of Public Health and Community Medicine, Sahlgrenska Academy - Gothenburg - Sweden ,

European Journal of Heart Failure Abstracts Supplement ( 2016 ) 18 ( Supplement 1 ), 284

Purpose: Although diabetes, hyperglycemia and insulin resistance increases risk of future cardiovascular disease (CVD), earlier genetic studies have failed to shown associations between diabetes related SNPs and CVD-risk. Here we set out to examine if 43 single-nucleotide polymorphisms (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 heart disease as measured by echocardiographical examination (UCG). 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). 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 common variants in 4 genes were associated (p < 0.05) with increased risk of prevalent diastolic dysfunction (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). The genetic risk scores (GRS) of the 4 SNPs associated with increased risk of DD and the 4 SNPs associated with decreased risk of DD association with prevalent DD were (OR = 1.19, 95% CI 1.08-1.32, p = 0.001) and (OR = 0.82, 95% CI 0.74-0.91, p=1,4x10-4), respectively. Furthermore, common variants in 3 genes were associated (p < 0.05) with decreased risk of prevalent left ventricular hypertrophy (LVH) (HNF1A (OR, 0.67, p = 0.001), ADAMTS9 (OR, 0.79, p = 0.038), GIPR (OR, 0.74, p = 0.018). The GRS of these 3 SNPs was also highly significantly associated with decreased LVH risk (OR = 0.74, 95% CI 0.64-0.85, p=3.1x10-5). Conclusion: Here we show that identified in GWAS T2D and glycemic traits susceptibility loci are associated with both increased and decreased risk of structural heart abnormalities as measured by UCG. Replication of these findings is presently ongoing in an independent Swedish cohort.

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