ECE2019 Poster Presentations Diabetes, Obesity and Metabolism 1 (104 abstracts)
Diabetes-, sex-, and BMI specific associations of genetic variants in PRRG1 with cardiovascular surrogates in a large cohort at CV risk
Natascha Schweighofer 1, , Christoph W Haudum 1, , Albrecht Schmidt 3 , Ewald Kolesnik 3 , Caterina R Colantonio 3 , Burkert Pieske 3 , Thomas R Pieber 1, & Barbara Obermayer-Pietsch 1
1Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria; 2CBmed GmbH, Center for Biomarker Research in Medicine, Graz, Austria; 3Department of Internal Medicine, Division of Cardiology, Medical University of Graz, Graz, Austria.
The proline rich and Gla domain genes PRRG1-4 encode for short transmembrane proteins. PRRG proteins contain a Gla domain with glutamic acid residues which are gamma-carboxylated in a vitamin-K-depend manner. In a previous study, we were able to show a decrease in PRRG1 gene expression during intima thickening in atherosclerosis. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in the vitamin-K-dependent protein PRRG1 with cardiovascular parameters (pathologic intima media thickness (IMT), left atrial volume index (LAVI), left ventricular mass index (LVMI) or pulse wave velocity (PWV), and relative wall thickness (RWT) groups) in three diabetes stages (no diabetes, prediabetes and type 2 diabetes), in lean and overweight persons and males vs. females. We investigated the BioPersMed cohort (n=1025), a prospective cohort study of asymptomatic patients with one cardiovascular risk factor. Determination of PRRG genotypes was done by GSA array (Illumina Inc., USA). Pulse wave analysis was done using a SphygmoCor device (Atcor Medical, Australia) and echocardiographic measurements were performed using the Vivid 9 device (GE Healthcare Austria GmbH & Co OG, Austria). Type 2 diabetes (T2DM) and prediabetes were defined according to ADA criteria. Persons with a BMI < 25 were defined as lean. RWT groups showed concentric (>0.42) or eccentric (≤0.42) hypertrophy. A LAVI <29 ml/m2, a LVMI ≥ 96 (females) or 116 (males) g/m2, an IMT > 0.9 mm and a PWV < 10 m/s (end organ damage) were considered pathologic. No associations were seen with these SNPs and parameters in the other patients’ groups (data not shown). Chi-square analysis revealed significant associations of PRRG1 SNPs in females and males with RWT groups. These associations might implicate a possible role of PRRG1 and vitamin K-dependent proteins in the modulation of important cardiovascular parameters and thus contribute to cardiovascular risk.
| no diabetes | pre-diabetes | T2DM | lean | overweight | |||||
| ID of genetic variation | IMT | LVMI | LAVI | RWT group | PWV | LAVI | LVMI | RWT group | LVMI |
| rs113362444 | 0.034 | 0.002 | ns | 0.028 | 0.020 | 0.059 | 0.076 | ns | 0.003 |
| rs5917507 | 0.063 | 0.017 | 0.015 | 0.009 | 0.059 | 0.046 | ns | 0.025 | 0.027 |
| kgp22829647 | 0.063 | 0.013 | 0.018 | 0.008 | 0.047 | 0.048 | ns | 0.010 | 0.014 |
| kgp22738694 | 0.094 | 0.028 | ns | 0.050 | ns | 0.041 | ns | 0.002 | 0.012 |
| rs5917212 | 0.038 | 0.083 | ns | 0.049 | 0.067 | 0.073 | 0.035 | 0.002 | 0.099 |
| rs6610168 | 0.037 | 0.085 | ns | 0.048 | 0.075 | 0.066 | 0.038 | 0.004 | 0.087 |
| kgp22730765 | 0.010 | Ns | ns | 0.039 | ns | ns | 0.094 | ns | 0.082 |
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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