Hypertension Subtypes and Angiotensin Converting Enzyme (ACE ...

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lady, subjects of extremes of age ( 75 years) and participants under antihypertensive medication were excluded from the study. Information on ...
© JAPI • june 2012 • VOL. 60

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Original Article

Hypertension Subtypes and Angiotensin Converting Enzyme (ACE) Gene Polymorphism in Indian Population PK Boraha, P Shankarishana, NC Hazarikab, J Mahantaa Abstract Objective: To find out the association of angiotensin converting enzyme (ACE) gene polymorphism with hypertension subtypes in a population from India. Methods: Consecutive subjects of either sex, aged ≥ 18 years attending in temporary field clinics arranged in various localities of Assam and Mizoram were interviewed to record information about socio-demographic characteristics, alcohol consumption and smoking. Three readings of blood pressure, height and weight of all subjects were measured. Hypertension and its subtypes were defined as per JNC-VI criteria. Fasting venous blood samples were collected to estimate blood glucose level and to extract genomic DNA followed by PCR analysis for ACE gene polymorphism. Results: A total of 916 (Male=465, Female=451) consecutive subjects comprising of 407 (44.4%) hypertensive subjects and 509 (55.6%) normotensive controls were included in the study. Of the hypertensive subjects, majority (69.0%) had systolic diastolic hypertension with male predominance (70.3% vs. 67.6%) which was followed by isolated diastolic hypertension (16.7%) and isolated systolic hypertension (14.3%). The predominant ACE genotype was Ins/Ins (50.0%) and Del/Del genotype showed lowest prevalence (11.4%). After adjusting confounding variables, the Del/Del genotype revealed significant association with isolated systolic hypertension. Conclusion: Del/Del polymorphism of ACE gene showed significant association with ISH in our study population.

I

Introduction

solated or combined elevations of systolic and diastolic blood pressure (BP) leading to development of different hypertension subtypes reflects distinct patho-physiological mechanisms, prognostic implications and requires different therapeutic approach for each subtype.1 Studies performed elsewhere revealed an age-dependent increase in both systolic and diastolic blood pressure (SBP and DBP) up to the 6th decade of life,2 after that only systolic pressure continues to rise and DBP remains stable or tend to show slight decline. As such, isolated diastolic hypertension (IDH) is the major event in the earlier age of life whereas isolated systolic hypertension (ISH) predominates in older age groups leading to increase cardiovascular morbidity and mortality.3 Environmental4 or genetic factors like polymorphism of genes encoding various proteins of renin angiotensin system (RAS)5 might be responsible for such age related change in blood pressure. The gene encoding angiotensin converting enzyme (ACE) of RAS is polymorphic and shows inconsistent association with BP.6 Population based studies showed the effect of ACE insertion/ deletion (Ins/Del) polymorphism on the blood pressure levels in men7,8 and higher prevalence of hypertension in smokers with D allele.9 In addition to its association with hypertension, ACE gene polymorphism independently modulated age related increase in pulse pressure (PP) with significantly higher slope of age-PP and age-SBP relationships for deletion/deletion (Del/Del) than other genotypes.10 In the present communication we studied distribution of ACE genotypes in a population from North Eastern region of India to find out any significant association with various hypertension subtypes.

Materials and Methods

Temporary field clinics for general health check up were organized at small localities of two states (Assam and Mizoram) a Regional Medical Research Centre, NE Region (ICMR), Dibrugarh, Post Box-105, Assam; bState Institute of Health and Family Welfare, G.S. Road, Khanapara, Guwahati, Assam Received: 18.06.2010; Revised: 21.07.2011; Re-revised: 23.08.2011; Accepted: 24.08.2011

to examine the study participants. Selection of field sites was based on technical feasibility and easy accessibility. Consecutive subjects of either sex aged 18 years and above and providing informed consent were included in the study. However, pregnant lady, subjects of extremes of age ( 75 years) and participants under antihypertensive medication were excluded from the study. Information on demographic variables including age, gender and cardiovascular risk factors like habit of smoking and alcohol consumption were collected using a pre-structured and pretested questionnaire. Blood pressure was recorded using a random zero sphygmomanometer with appropriate cuff size. Three measurements at an interval of five minutes were taken in sitting position after allowing the person to rest for a minimum period of five minutes. Recording of blood pressures from subjects taking any sort of alcoholic beverage or smoking within two hours of blood pressure measurement were avoided. SBP was recorded on the appearance of first Korotkoff sound and DBP was recorded during fifth Korotkoff phase. We adopted JNC-VI guidelines11 to define hypertension and its subtypes. Accordingly, hypertension was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg or under antihypertensive medications. Hypertension subtypes was classified into ISH (SBP ≥ 140 mmHg and DBP

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