Target Organ Damage Of Various Pra In Hypertensive Patients And The Association Study Between Various PRA And ADRPK1 Gene

Objective: Essential hypertension is one of common cardiovascular diseases that threaten human health and may lead to a serial of severe results such as cardiac and renal failure and stroke. Hypertension is a set of clinical syndrome that can be divided into different subtypes. Mechanisms of hypertension with subtypes are different. From pathophysiology, essential hypertension can be divided into renin dependence of hypertension and salt-volume dependence of hypertension by plasma renin activity. HOPE study showed that in patients with atherosclerosis and diabetes, high renin activity levels is major independent risk factors for cardiovascular events and all-cause death. Renin, which is mostly produced by the juxtaglomerular cells of the kidney, converts angiotensinogen to angiotensin I, which is the first and rate-limiting step of the RAAS cascade. Renin is a major regulator of blood pressure through its modulation of salt and water homeostasis and angiotensinâ…¡. And epithelial sodium channels(ENa C) plays an important role in the process of regulating water and salt metabolism balance. Beta-adrenergic receptor kinase 1(ADRBK1) by mediating ENa C expression and degradation regulate blood pressure. It is a candidate gene of hypertension. On the basis of previous work, various renin in hypertensive patients have different genetic mechanism, esstissioal hypertension were divided into four subgroups besed PRA by quartile. In our study, we investigate clinical characteristics of various renins in hypertensive patients and association with PRA and target organ damage of hypertensive, including left ventricular hypertrophy and early kidney damage. Forthmore, it would be explore the potential association between genetic variation of ADRBK1 and various renin hypertensive patients(high-renin, medium-renin, and low-renin). And it would indicative the different genetic mechanism of hypertension in various PRA and get a new method to prevent and control blood pressure. Methods: 1) This cross-sectional study included a total of 1831 Han patients diagnosed essential hypertension who were hospitalization at Department of Hypertension in people’s Hospital of Xinjiang Uygur Autonomous Region in China, subjects aged more than 30 years and less than 60 years. There is no history of miscegenation within three generations. All data, including age, gender, blood lipid and other general clinical phenotype were acquired from all subjects.Following an overnight fasting, blood samples were obtained from an antecubital vein in a sitting position after at least 15 minutes of rest at 9 AM. After recruited, sitting PRA was tested in hypertensive patients and hypertensive patients were stratified into four renin categories by its quartile, as following: quartile 1 group, < 0.44ng/m L/h, n=457; quartile 2 group, 0.44 to 1.07ng/m L/h, n=458; quartile 3 group, 1.08 to 2.36ng/m L/h, n=456; and quartile 4 group,>2.36ng/m L/h, n=460 based on sitting PRA. 2) 879 cases that tested echocardiography and ambulatory blood pressure from the first part were recruited. Cut-off points of renin groups were consistent with the first part. To analyse association different PRA level patients and EH with left ventricular hypertrophy, and explore the effect of the setting plamse renin activity on EH with left ventricular hypertrophy(LVH). 3) 1614 cases that tested echocardiography and ambulatory blood pressure from the first part were recruited. Cut-off points of renin groups were consistent with the first part. To analyse association different PRA level patients and EH with early renal damage, and explore the effect of the setting plamse renin activity on EH with early renal damage. 4) In this study, we collected 1831 patients with EH as EH group and 426 health people with normotension as control group. Representative variations were selected from database and genotyped with Taq Man polymerase chain reaction method. For the relatively isolated population from a homogeneous environment, a case-control study was conducted to assess the association between variations of ADRBK1 gene and hypertension. 5) Hypertensive patients were classified into four renin categories via PRA quartile. Such single nucleotide polymorphisms(SNPs) of ADRBK1 gene as rs1894111, rs4930416, rs7127431 were identified via Taq Man polymerase chain reaction in four groups. Results: 1) the plasma renin activity have differences statistically significant between male and female(P<0.05); Plasma renin activity has differences statistically significant in 30 to 40 years, 40 to 50 years and 50 to 60 years group(P<0.05); According to sitting PRA, EH patients were divided into four groups by quartile. there is statistically significant difference in male, age, height, weight, waist circumference, smoking, drinking, family history, office systolic blood pressure, office diastolic blood pressure, PRA, PAC, ARR ratio, TC, TG, LDL- C and dyslipidemia from the four groups(P<0.05). 2) The difference of interventricular septum thickness, left ventricular posterior wall thickness, LVMI in four groups were statistical significance(P<0.05). the difference incidence of LVH and left ventricular configuration such as normal geometry(NG), concentric remodeling(CCR), concentric hypertrophy(CCH), and eccentric hypertrophy(ECH) in four groups were statistical significance(P<0.05). partial correlation analysis showed that: adjusting with gender, age, BMI, serum sodium, HDL-C, TC, LDL-C, TG, 24 h MAP, and 24 h average heart rate, PRA was correlated with interventricular septum thickness, left ventricular posterior wall thickness, and LVMI(P<0.05). Regression analysis showed that: with Lg LVMI as dependent variable, PRA was correlated with LVMI(OR=0.115, 95%CI0.002~0.007, P=0.002). With LVH/no-LVH as dependent variable, PRA was correlated with LVH(OR=1.163, 95%CI 1.065~1.271, P=0.001). According to multiple logistic regression analysis, high-renin groups were associated with a higher resk for LVH(OR=2.268, 95%CI 1.256~4.100 P=0.007). 3) In four groups of Creatinine, Cyst C have differences statistical significance(P<0.05). Logistic regression showed that Cyst C as dependent variable, adjusted gender, BMI, course, office systolic pressure, office diastolic blood pressure and high renin group were associated with high risk for Cyst C(OR=0.491, 1.390, 1.330, 1.016, 0.981, 2.087). 4) In the Han population in Xinjiang, compared with the control, CT+TT genotypers and T allele frequency distribution of rs1894111 were significantly higher than control group(P < 0.05). No significant difference of the rs7127431å'Œrs4930416 were found between the EH patients and control subjects(P>0.05).After adjust gender, age and body mass index(BMI), the frequency distribution of dominant model(CC vs. CT+TT) of rs1894111 in different level of systolic blood pressure(SBP) also showed significantly statistical difference(136.19±19.90 vs. 139.19±20.90, P < 0.05). The frequency of haplotype H1(rs7127431C-4930416As1894111C) in EH group was lower than control group(87.8% vs. 89.6%), and reverse in the frequency of haplotype H2(rs7127431C-4930416A-s1894111T), 5.8% and 3.4%, respective(P<0.05). After adjust gender, age and BMI, the multiple logistic regression indicated that the CT+TT genotype of rs1894111 variation was a risk factor of EH(OR=1.771, 95%CI=1.092~2.871, P=0.02). 5) Distribution of genotype and allele of rs1894111 showed significant differences between hypertensive and control group(P<0.05). Moreover, distribution of dominant model(CC vs. CT+TT) in rs1894111 was lower in hypertensive group than in control group(P<0.05). While subjects were classified into four subgroups based on PRA quartile, dominant model(CC vs. CT+TT) of rs1894111 was found significantly lower in quartile 1 group, the group with the lowest PRA, than in control group(P<0.05). Logistic regression analysis demonstrated that dominant model(CC vs. CT+TT) of rs1894111 was significant differences in hypertensive group(OR=1.590, 95%CI=1.022-2.474, P<0.05), particularly in quartile 1 group(OR=1.845, 95%CI=1.119-3.042, P<0.05), but not in quartile 4 group. Conclusion: 1) Setting plasma renin activity level in famale is less than in male, and plasma aldosterone concentration in famale is more than in male. With aging, setting plasma renin activity level was descent and ARR ratio was increaseed.The male, smoking, alcohol, abdominal circumference, and dyslipidemia of high-renin are more than that of low-renin group, and age, history of hypertension, and durning of high-renin group are more than that of low-renin group. 2) The plasma renin activity is a risk factor for EH with left ventricular hypertrophy. High-renin group is 2.269 times risk of low-renin group in concurrent of EH with LVH, and High-renin group is high incidence of ECH. 3) PRA is a risk factor for hypertensive patients with early renal damage. High-renin group is higher than low-renin groups in the Cyst C of early renal damage. 4) The gene polymorphism of ADRBK1 may be associated with EH, and the CT+TT genotype of rs1894111 variation could be a risk factor of EH. 5) Genetic polymorphisms of ADRBK1 might be associated with low-renin hypertension in Han Chinese.