Association Of The 217a Variant Of Agt Gene With Hypertension

Because hypertension is more common in African-American subjects, our laboratory is interested in understanding molecular mechanisms involved in hypertension in the African-American population. We have therefore analyzed 186 African-American and 127 Caucasian subjects with hypertension (mean age: 59 ± 10 yr) and 156 African-American and 135 Caucasian normotensive controls (mean age 58 ± 10 yr). All of these subjects were recruited from the outpatient department of The State University of New York Health Science Center in Brooklyn, New York and Westchester Medical Center, Valhalla, New York. All case and control subjects gave informed consent before participating in the research. All cases were diagnosed as having primary hypertension and patients with secondary hypertension, diabetes mellitus, or ischemic heart disease were excluded. The criteria for hypertension was defined as a SBP greater than 140 mmHg, a DBP greater than 90 mmHg, or under antihypertensive therapy. BP was measured twice with the subject seated and a 5-min interval between measurments. The normotensives (with SBP/DBP <140/90 mmHg) without a history of hypertension and without diabetes mellitus were recruited from the same population and matched for sex and age. All participants completed a standard questionnaire on personal medical history and family history of hypertension. All patients and control subjects were in Hardy-Weinberg equilibrium. The frequency of the -217A allele in hypertensive patients was 0.29 as compared with 0.19 in the normotensive population, which is highly significant (p = 0.0017 and OR =1.792) (Table 1). To compare the role of this polymorphic site on hypertension in the African-American and Caucasian populations, we also analyzed genomic DNA from 127 Caucasian hypertensive subjects and 135 normotensive controls. The frequency of -217A allele was 0.15 in Caucasian hypertensive subjects and 0.11 in normotensive controls which is not significant (p = 0.12) (Table 1). Statistical analysis based on the -217 A/G genotype (using A allele as a dominant model) also suggested a significant role of the -217A allele in hypertension in African-Americans (p = 0.0021 and OR = 2.015) and not in Caucasians (Table 2). Because an A/G polymorphism at -6 has previously been associated with hypertension, we also analyzed genomic DNA from the African-American and Caucasian populations for this polymorphism. The frequency of -6A allele was 0.87 in African-American hypertensive subjects and 0.85 in normotensive controls, which was not significant (p = 0.58). However, the frequency of -6A allele was marginally significant in Caucasian subjects (p = 0.06). These experiments suggested that -217A allele of the human AGT gene plays a significant role in essential hypertension in African-Americans (41). However, if we double the number of total Caucasian subjects, then the role of -217A becomes significant. It is therefore possible that this polymorphism will be significant in Caucasian subjects if we analyze more samples.

Table 1

Statistical Analysis of -217 A/G Polymorphism of Human Angiotensinogen Based on Allele Frequency

A allele

G allele p value

African-American hypertensive (n = 186)

Normotensive (n = 156) Caucasian hypertensive (n = 127) Normotensive (n = 135)

Table 2

Statistical Analysis of -217 A/G Polymorphism of Angiotensinogen Gene Based on the Genotype Distribution Using A Allele Dominant Model

p value

African-American hypertensive (n = 186) 12 84 90

Normotensive (n = 156) 4 50 102 Caucasian hypertensive (n = 127) 4 31 92

Normotensive (n = 135) 3 23 109

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