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Alpha Adducin (ADD1) Gene Polymorphism and New Onset of Diabetes Under the Influence of Selective Antihypertensive Therapy in Essential Hypertension.

ABSTRACT: BACKGROUND:Different antihypertensive therapies (especially diuretics) are reported to induce the new onset of diabetes in some hypertensive patients. ?-adducin-1 (ADD1) gene is salt sensitive gene which has its role in etiology of hypertension via salt sensitivity. Therefore, the G460T polymorphism of ADD1 gene may be associated with new onset of diabetes under the influence of diuretic and other antihypertensive therapies. AIM:To assess the correlation between genetic polymorphism (ADD1 G460T polymorphism) and glycaemic disturbance under influence of diuretic and other antihypertensive drug therapies. MATERIALS AND METHODS:We recruited study subjects, 270 normotensive as control (150 male and 120 females), 270 hypertensive patients (95 male and 175 females) and 240 hypertensive with new onset of diabetes patients (80 male and 160 females). All study samples were genotyped for ADD1 polymorphic alleles and analyzed the relationship between different genotypes with respect to anthropometric and clinical parameters along with drug therapies. RESULTS:Clinical and anthropometric parameters (such as age, SBP, DBP, FBG, height, weight, WC, HP, W/H ratio, and BMI) of study population were found highly statistically significant (p<0.05) at base value. Further, genotype wise comparison of all the above parameters revealed most of them as non-significant (p>0.05). Whereas, comparison between genotype and different antihypertensive drug therapy of hypertensive patients, specifically, diuretic therapy as mono in male (p=0.0227) and female (p=0.0292) and in combination with BBs in both male (p=0.0023) and female (p=0.0079) revealed a higher FBG level in variant T allele. In case of hypertensive with new onset of diabetes patients, only female population showed a slightly statistically significant (p=0.0413) difference in FBG level with diuretic mono therapy. Other antihypertensive drug therapies were safe and effective either as mono or in combination therapy. DISCUSSION:Anthropometric parameters may be the indicative factors for hypertension and diabetes. Variant T allele of ADD1 gene may be considered as the risk factor for the development of diabetes in hypertensive patients. Diuretics as mono therapy and in combination with BBs may be considered as the risk factor for new onset of diabetes in EH patients carrying variant T allele (either as TG or TT).

SUBMITTER: Gupta S

PROVIDER: S-EPMC6635650 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Alpha Adducin (ADD1) Gene Polymorphism and New Onset of Diabetes Under the Influence of Selective Antihypertensive Therapy in Essential Hypertension.

Gupta Sumeet S Jhawat Vikas V Agarwal Bimal Kumar BK Roy Partha P Saini Vipin V

Current hypertension reviews 20190101 2

<h4>Background</h4>Different antihypertensive therapies (especially diuretics) are reported to induce the new onset of diabetes in some hypertensive patients. α-adducin-1 (ADD1) gene is salt sensitive gene which has its role in etiology of hypertension via salt sensitivity. Therefore, the G460T polymorphism of ADD1 gene may be associated with new onset of diabetes under the influence of diuretic and other antihypertensive therapies.<h4>Aim</h4>To assess the correlation between genetic polymorphi ...[more]

PMID: 30062972

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Project description:Tribbles homolog 3 (TRIB3) mediating signaling pathways are closely related to blood pressure regulation. Our previous findings suggested a greater benefit on vascular outcomes in patients carrying TRIB3 (251, A > G, rs2295490) G allele with good glucose and blood pressure control. And TRIB3 (rs2295490) AG/GG genotypes were found to reduce primary vascular events in type 2 diabetic patients who received intensive glucose treatment as compared to those receiving standard glucose treatment. However, the effect of TRIB3 genetic variation on antihypertensives was not clear in essential hypertension patients. A total of 368 patients treated with conventional dosage of antihypertensives (6 groups, grouped by atenolol/bisoprolol, celiprolol, doxazosin, azelnidipine/nitrendipine, imidapril, and candesartan/irbesartan) were enrolled in our study. Genetic variations were successfully identified by sanger sequencing. A linear mixed model analysis was performed to evaluate blood pressures among TRIB3 (251, A > G) genotypes and adjusted for baseline age, gender, body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol and other biochemical factors appropriately. Our data suggested that TRIB3 (251, A > G) AA genotype carriers showed better antihypertensive effect than the AG/GG genotype carriers [P = 0.014 for DBP and P = 0.042 for mean arterial pressure (MAP)], with a maximal reduction of DBP by 4.2 mmHg and MAP by 3.56 mmHg after azelnidipine or nitrendipine treatment at the 4th week. Similar tendency of DBP-change and MAP-change was found for imidapril (ACEI) treatment, in which marginally significances were achieved (P = 0.073 and 0.075, respectively). Against that, we found that TRIB3 (251, A > G) AG/GG genotype carriers benefited from antihypertensive therapy of ARBs with a larger DBP-change during the period of observation (P = 0.036). Additionally, stratified analysis revealed an obvious difference of the maximal blood pressure change (13 mmHg for the MAP between male and female patients with AA genotype who took ARBs). Although no significant difference in antihypertensive effect between TRIB3 (251, A > G) genotypes in patients treated with α, β-ADRs was observed, we found significant difference in age-, sex-dependent manner related to α, β-ADRs. In conclusion, our data supported that TRIB3 (251, A > G) genetic polymorphism may serve as a useful biomarker in the treatment of hypertension.

Project description:BackgroundAntihypertensive drug therapies have been reported to be associated with new onset of type 2 diabetes mellitus in some hypertensive patients after prolonged use. Angiotensin converting enzyme (ACE) gene has been found to affect essential hypertension, response of antihypertensive therapies, and glycemic disturbances. Therefore, ACE gene I/D polymorphism may be associated with risk of new onset of type 2 diabetes via metabolic disturbances, glycemic dysregulation, and insulin resistance.AimTo assess the correlation between ACE gene I/D polymorphism and glycemic disturbance under influence of diuretic and other antihypertensive drug therapies.Materials and methodsWe recruited 270 normotensive patients as control (150 men and 120 women), 270 hypertensive patients (95 men and 175 women), and 240 hypertensive with new onset of diabetes patients (80 men and 160 women). All samples were genotyped for ACE gene polymorphic alleles and relationship between different genotypes and anthropometric and clinical parameters along with drug therapies was established and analyzed.ResultsBaseline clinical (systolic blood pressure, diastolic blood pressure, and fasting blood glucose level) and anthropometric parameters (height, weight, waist circumference, hip circumference, waist-hip ratio, and body mass index) of study populations were found highly statistically significant (P < .05) when compared among study groups. Furthermore, genotype wise comparison of all these parameters in essential hypertensive (EH) and essential hypertensive with onset of diabetes (EHNOD) patients found most of them nonsignificant and no variation was found with respect to different genotypes of ACE gene. The genotype wise comparison of clinical parameters among different antihypertensive drug therapy was found statistically nonsignificant in both EH and EHNOD patients.DiscussionAnthropometric parameters can be taken as the risk indicator factors for hypertension and diabetes. However, ACE gene polymorphism may not be a risk factor for development of diabetes in hypertensive patients.ConclusionThe present study suggested that ACE gene polymorphism did not show any significant association with the risk of new onset of diabetes in EH patients and more detailed studies with large population size are needed.

Project description:BACKGROUND:Hypertension is a modifiable cardiovascular risk factor implicated in neurodegeneration and dementia risk. In Huntington's disease, a monogenic neurodegenerative disease, autonomic and vascular abnormalities have been reported. This study's objective was to examine the relationship between hypertension and disease severity and progression in Huntington's disease. METHODS:Using longitudinal data from the largest worldwide observational study of Huntington's disease (n = 14,534), we assessed the relationship between hypertension, disease severity, and rate of clinical progression in Huntington's disease mutation carriers. Propensity score matching was used to statistically match normotensive and hypertensive participants for age, sex, body mass index, ethnicity, and CAG length. RESULTS:Huntington's disease patients had a lower prevalence of hypertension compared with age-matched gene-negative controls. Huntington's disease patients with hypertension had worse cognitive function, a higher depression score, and more marked motor progression over time compared with Huntington's disease patients without hypertension. However, hypertensive patients taking antihypertensive medication had less motor, cognitive, and functional impairment than Huntington's disease patients with untreated hypertension and a later age of clinical onset compared with untreated hypertensive patients and normotensive individuals with Huntington's disease. CONCLUSIONS:We report the novel finding that hypertension and antihypertensive medication use are associated with altered disease severity, progression, and clinical onset in patients with Huntington's disease. These findings have implications for the management of hypertension in Huntington's disease and suggest that prospective studies of the symptomatic or disease-modifying potential of antihypertensives in neurodegenerative diseases are warranted. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

Alpha Adducin (ADD1) Gene Polymorphism and New Onset of Diabetes Under the Influence of Selective Antihypertensive Therapy in Essential Hypertension.

Publications

Alpha Adducin (ADD1) Gene Polymorphism and New Onset of Diabetes Under the Influence of Selective Antihypertensive Therapy in Essential Hypertension.

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