Sumeet Gupta*, Vikas Jhawat, Bimal Kumar Agarwal, Partha Roy and Vipin Saini Pages 123 - 134 ( 12 )
Background: 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.
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).
Hypertension, antihypertensive therapy, diuretics, new onset of diabetes alpha adducing gene (ADD1), gene polymorphism, pharmacogenomics.
Department of Pharmacology, M. M. College of Pharmacy, M. M. (Deemed to be University), Mullana, (Ambala), Haryana, Department of Pharmaceutical Sciences, G . D Goenka, Gurugram, Haryana, Department of Medicine, M. M. Institute of Medical Sciences and Research, M. M. (Deemed to be University), Mullana, (Ambala), Haryana, Department of Biotechnology, Indian Institute of Technology Roorkee, Uttarakhand, M. M. Medical College & Hospital, Kumarhatti, Solan, Himachal Pardesh