Non-dipping and arterial hypertension depend on clinical factors rather than on genetic variability of ACE and RGS2 genes in patients with type 1 diabetes

Abstract

The aim of our study was to characterize the association of clinical and genetic risk factors such as: ACE genotype (rs17997552, rs1800764, rs4459609) and RGS2 (rs2746071) with the development of hypertension (HT) and non-dipping phenomenon in patients with type 1 diabetes mellitus (T1DM). A total of 238 adolescents and young adults with T1DM—103 females and 135 males, aged 8–30 years (mean 17.35 ± 5.2) with diabetes duration 1–26 years (mean 7.72 ± 6.2), with mean HbA1c (IFCC) 58 ± 15 mmol/mmol—were subjected to 24-h ambulatory blood pressure measurements (ABPM). The results of the ABPM were analyzed in association with the polymorphisms of ACE and RGS2 genes and clinical data of patients. HT was recognized in 65 (27 %) and non-dipping in 111 (46.63 %) patients. In the multivariate analysis of factors predisposing to HT, the variables that remained significant were the following: male sex (OR 1.62; 95 % CI 1.171–2.250), non-dipping (OR 1.40; 95 % CI 1.03–1.90) and total cholesterol level (OR 1.01; 95 % CI 1.005–1.021). The only factor influencing non-dipping was the duration of diabetes—OR 1.09 (95 % CI 1.04–1.14). The patients displaying non-dipping have a twice increased risk of development of HT (OR 2.17; 95 % CI 1.21–3.89). There was no association between disturbances of blood pressure (BP) and genotypes of ACE: rs17997552, rs1800764, rs4459609 and RGS2: rs2746071. Clinical rather than genetic risk factors seem to be connected with BP disturbances in young patients with T1DM. Although we have identified representative groups of HT versus non-HT and dipping versus non-dipping subjects, the effect of genetic predisposition to the development of higher BP is too weak to be statistically significant.Electronic supplementary materialThe online version of this article (doi:10.1007/s00592-014-0568-0) contains supplementary material, which is available to authorized users.

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

“…Thus, abnormal signaling pathways in the kidney of RGS2 À/À mice could impair water and solute processing. The authors of the original study of the hypertension of RGS2 À/À mice hypothesized that the differential acute changes in blood pressure between WT and RGS2-deficient mice to vasoconstrictor antagonists argued against plasma volume changes in RGS2 À/À mice as the primary cause of hypertension (Deja et al, 2014;Gurley et al, 2010;Heximer et al, 2003;Kvehaugen et al, 2014Kvehaugen et al, , 2013Nance et al, 2013;Zhang et al, 2013). One study has shown no difference in renal sympathetic activity in WT or RGS2 À/À mice (Tank et al, 2007).…”

“…One study has shown no difference in renal sympathetic activity in WT or RGS2 À/À mice (Tank et al, 2007). Although the significance of the renal abnormalities in the absence of RGS2 for regulation of plasma volume and systemic blood pressure is far from clear, its role in renal water and salt handling has been intensively studied with genetic correlations between RGS2 and the association of hypertension in humans (Deja et al, 2014;Kvehaugen et al, 2014Kvehaugen et al, , 2013Nance et al, 2013;Osei-Owusu et al, 2012;Sjogren et al, 2012;Zhang et al, 2013). Third, RGS2 exerts control over vascular tone through an interaction with a component of the nitric oxide (NO) pathway, protein kinase G (PKG)/cGMP-dependent protein kinase, which influences vascular relaxation mediated by NO (discussed in detail below) (Sun et al, 2005;Tang et al, 2003).…”

Mice overexpressing chromogranin A display hypergranulogenic adrenal glands with attenuated ATP levels contributing to the hypertensive phenotype

“…Nondipper hypertension is frequently accompanied by endothelial dysfunction and activation [40,41]. Type 1 diabetic patients who did not display dipping showed a two-fold increase in risk of developing hypertension [42]. Among patients with postural tachycardia syndrome, a nondipping BP profile is associated with a reduced orthostatic sympathetic reactivity not accounted for by autonomic neuropathy.…”

Angiotensin-converting enzyme insertion/deletion polymorphism, 24-h blood pressure profile and left ventricular hypertrophy in hypertensive individuals: a cross-sectional study

“…In the present study, the ACE I/D polymorphism had no influence on ND, which corroborates the results of other authors [ 21 , 23 ] although one study demonstrated a smaller drop between awake and sleep BP in hypertensive patients with the DD genotype in comparison to carriers of the I allele [ 44 ]. In addition, there was no effect of ACE I/D polymorphism or serum ACE levels on circadian variability of blood pressures among pediatric renal transplant patients [ 46 ] and in patients with type 1 diabetes [ 47 ].…”