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PROX1 gene variant is associated with fasting glucose change after antihypertensive treatment.

ABSTRACT: To assess the relationship of the 33 single nucleotide polymorphisms (SNPs) previously associated with fasting glucose in Caucasians in genome-wide association studies (GWAS) with glucose response to antihypertensive drugs shown to increase risk for hyperglycemia and diabetes.Randomized, multicenter clinical trial.A total of 456 Caucasian men and women with uncomplicated hypertension.The Pharmacogenomic Evaluation of Antihypertensives Responses study evaluated blood pressure and glucose response in uncomplicated hypertensive patients randomized to either atenolol or hydrochlorothiazide (HCTZ) monotherapy, followed by combination therapy with both agents. Association of these SNPs with atenolol- or HCTZ-induced glucose response was evaluated in 456 Caucasian patients using linear regression adjusting for age, sex, body mass index, baseline glucose, baseline insulin, and principal component for ancestry. The SNP rs340874 in the 5' region of PROX1 gene was significantly associated with atenolol-induced glucose change (p=0.0013). Participants harboring the C allele of this SNP had greater glucose elevation after approximately 9 weeks of atenolol monotherapy (? = +2.39 mg/dl per C allele), consistent with the direction of effect in fasting glucose GWAS, that showed the C allele is associated with higher fasting glucose.These data suggest that PROX1 SNP rs340874, discovered in fasting glucose GWAS, may also be a pharmacogenetic risk factor for antihypertensive-induced hyperglycemia. ?-blockers and thiazides may interact with genetic risk factors to increase risk for dysglycemia and diabetes.

SUBMITTER: Gong Y

PROVIDER: S-EPMC3945213 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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PROX1 gene variant is associated with fasting glucose change after antihypertensive treatment.

Gong Yan Y McDonough Caitrin W CW Beitelshees Amber L AL Karnes Jason H JH O'Connell Jeffrey R JR Turner Stephen T ST Chapman Arlene B AB Gums John G JG Bailey Kent R KR Boerwinkle Eric E Johnson Julie A JA Cooper-DeHoff Rhonda M RM

Pharmacotherapy 20131009 2

<h4>Study objective</h4>To assess the relationship of the 33 single nucleotide polymorphisms (SNPs) previously associated with fasting glucose in Caucasians in genome-wide association studies (GWAS) with glucose response to antihypertensive drugs shown to increase risk for hyperglycemia and diabetes.<h4>Design</h4>Randomized, multicenter clinical trial.<h4>Patients</h4>A total of 456 Caucasian men and women with uncomplicated hypertension.<h4>Measurements and main results</h4>The Pharmacogenomic ...[more]

PMID: 24122840

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Project description:The pattern of the left ventricle (LV) has important significance in adults with hypertension. The aim of the present study was to analyze changes and determinants of LV geometry after 1 year of antihypertensive treatment in children with primary hypertension (PH) in relation to metabolic abnormalities and anthropometrical parameters. In 86 children (14.1 ± 2.4 years) with newly diagnosed PH, LV geometry and biochemical parameters before and after 12 months of standard antihypertensive therapy were assessed. At baseline, normal LV geometry (NG) was found in 42 (48.9%), concentric remodeling (CR) in 4 (4.6%), concentric hypertrophy (CH) in 8 (9.3%), and eccentric hypertrophy (EH) in 32 (37.2%) patients. The prevalence of NG in patients with severe hypertension was significantly lower than in patients with ambulatory hypertension. There were no differences in dipping status in relation to LV geometry. Patients with CH and EH were more viscerally obese than patients with NG. Patients with CH had higher diastolic blood pressure in comparison with EH patients (p < 0.05). The main predictor of relative wall thickness (RWT) was the triglycerides to high density lipoprotein cholesterol (TG/HDL) ratio (R(2 ) = 0.319, β = 0.246, p = 0.004). Patients received 12 months of antihypertensive treatment, either lifestyle modification only (n = 37) or lifestyle modification plus antihypertensive medications (n = 49) if severe ambulatory hypertension or target organ damage were present. After 12 months of treatment the prevalence of EH (37.2% vs 18.6%, p = 0.003) decreased but prevalence of CH did not change. Patients in whom RWT decreased also decreased waist circumference and TG/HDL; the main predictor of RWT decrease was a decrease of the TG/HDL ratio (β = 0.496, R (2) = 0.329, p = 0.002). In adolescents with PH, LV geometry is related to central obesity and insulin resistance. Decrease of abdominal obesity and insulin resistance are the most important predictors of normalization of LV geometry, however CH has lower potential to normalize LV geometry.

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PROX1 gene variant is associated with fasting glucose change after antihypertensive treatment.

Publications

PROX1 gene variant is associated with fasting glucose change after antihypertensive treatment.

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