Genetic Background of Hypertension in Connective Tissue Diseases

Abstract

Peroxisome proliferator-activated receptors (PPAR gamma-2) and beta-3-adrenergic receptors (ADRB3) are involved in the risk of hypertension. But their exact role in blood pressure modulation in patients with connective tissue diseases (CTD) is still not well defined. In this study, 104 patients with CTD and 103 gender-and age-matched controls were genotyped for Pro12Ala and C1431T polymorphisms of the PPAR gamma-2 gene and Trp64Arg polymorphism of the ADRB gene. Anthropometric and biochemical measurements were evaluated, followed by genotyping using TaqMan® SNP genotyping assays and polymerase chain reaction-restriction fragment length polymorphism. The prevalence of analyzed genotypes and alleles was comparable between patients with CTD and the control group, as well as hypertensive and normotensive subjects. Patients with CTD have lower body fat and higher body water amount, serum glucose, and triglyceride (TG) levels. Hypertensive subjects are older and have higher body mass, BMI, waist circumference (WC), body water content, glucose, and TG concentration. The multivariate analysis revealed that hypertensive subjects with Ala12/X or Trp64Trp have higher body mass and WC when compared to normotensive subjects. Trp64Trp polymorphism was also characterized by a higher TG level, while T1431/X subjects had higher WC. The presence of CTD, visceral fat distribution, and increased age are the predictors of hypertension development. Hypertensive patients with CTD and Trp64Trp polymorphism have an increased risk of visceral obesity development and metabolic complications, which in turn affects the value of blood pressure. In addition, either Ala12/X or T1431/X predicts the visceral body fat distribution in hypertensive subjects. gamma-2, the Trp64Arg polymorphism of the ADRB3 gene (e.g., Trp64Arg) influences metabolic parameters and cardiovascular risk [12].Since the ratio between polymorphisms of PPAR gamma-2 and ADRB3 genes is not well established in hypertensive patients with CTD, we tested whether analyzed genetic factors are associated with blood pressure values and metabolic parameters in this group. Therefore, we determined the frequency of the analyzed variants and polymorphisms of the PPAR gamma-2 gene in CTD patients, and we investigated their association with hypertension in the context of anthropometric and biochemical parameters.

Development of the prediction model for hypertension in patients with idiopathic inflammatory myopathies

“…A cross‐sectional study on adult dermatomyositis found that the prevalence of metabolic syndrome was higher than healthy controls (41.7% vs. 7.0%; P < .001), and prior hypertension may be closely related to the development of metabolic syndrome 32 . Diabetes mellitus, higher levels of TG, and LDL‐C are common in IIMs patients with hypertension, which are in accordance with the characteristics of hypertensive subjects with connective tissue diseases in previous study 33 . A multicenter study demonstrated that adult polymyositis and dermatomyositis had a higher prevalence of diabetes mellitus (13% vs. 0%; P < .007).…”

“… 32 Diabetes mellitus, higher levels of TG, and LDL‐C are common in IIMs patients with hypertension, which are in accordance with the characteristics of hypertensive subjects with connective tissue diseases in previous study. 33 A multicenter study demonstrated that adult polymyositis and dermatomyositis had a higher prevalence of diabetes mellitus (13% vs. 0%; P < .007). 7 Diabetes mellitus significantly increases the risk of developing hypertension in patients with polymyositis and dermatomyositis compared to controls (OR = 2.94, 95%CI: 2.04–4.23).…”

Functional Polymorphism in the ADRB3 Gene, Encoding the Beta-3 Adrenergic Receptor, and Response to Intra-Detrusor Injection of Botulinum Toxin-A in Women with Overactive Bladder

“…Under the above assumptions, the confidence interval of the minimum estimated sample size needed ranged from 1406 to 1524. We also want to emphasize that the prevalence of the ADRB3:c.190C allele in our cohort (5.6%) was smaller than those reported from studies carried out either on Polish women without OAB (from 8.6% to 10.3%) [32][33][34][35] or on other OAB patients of European descent (8.1%, 9.0%, and 10.8%) [13,14,36]. It is also worth noting that, to date, the association of ADRB3:rs4994 with a predisposition to OAB has been reported only by Ferreira et al for 49 Brazilian females (17 white women and 32 non-white women; the frequency of ADRB3:c.190C allele: 25.5%) [9] and by Honda et al for 100 Japanese females (the frequency of ADRB3:c.190C allele: 26.0%) [10].…”