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Angiotensin II type2 (AT2) receptor gene polymorphism and hypertension in the elderly with salty taste disturbance
80A
POSTERS: Genetics/Gene Therapy
Conclusion: The increase of non-dipper in the carrier of CC genotype was one of the reasons suggesting the genetic involvement of AGT polymorphism in the risk for cardiovascular disease.
AJH–April 2001–VOL. 14, NO. 4, PART 2
vs 57%, P⫽0.03), familial premature CV disease (65% vs 39%, P⫽0.02) and clinical systemic atherosclerosis [sys-ASO; ⬎ 1 anatomic location] (74% vs 41% P⫽0.002). The Table below summarizes the genetic profile of the subjects.
Key Words: angiotensinogen gene, 24hr blood pressure, genetic analysis Group A Group B
P-149 ANGIOTENSIN II TYPE2 (AT2) RECEPTOR GENE POLYMORPHISM AND HYPERTENSION IN THE ELDERLY WITH SALTY TASTE DISTURBANCE Shoroku Sakurai, Kohya Okaishi, Shigeto Morimoto. 1Department of Geriatric Medicine, Osaka University Medical School, Yamadaoka, Suita, Osaka, Japan Although hypertension in the elderly is highly dependent on excess intake of sodium, at least partially based on salty taste disturbance, little is known about association of gene polymorphisms with hypertension in the elderly with salty taste disturbance. To clarify the role of gene polymorphisms in this mechanism, 126 elderly female subjects and 61 male subjects were enrolled (mean age ⫹ SD; 81 ⫹ 7 years) for determination of magnitudes of NaCl (1.25%, 2.5%, 5%, 10% and 20%) in aqueous solution. Thresholds for salty taste were divided into six grades. Non of the subjects took angiotensin-I converting enzyme (ACE) inhibitors or angiotensin II type 1 (AT1) receptor antagonists. We analyzed A1166C polymorphism of human AT1 receptor gene, C3123A polymorphism of AT2 receptor gene mapped on human X chromosome, angiotensinogen M235T polymorphism, and angiotensin-I converting enzyme gene I/D polymorphism. There was a significant (female; p⫽0.005,male;p⫽0.040) association (ANOVA) of salty taste threshold with the AT2 receptor gene polymorphism, but not with other polymorphisms. Thus the elderly subject with AA genotype of the AT2 receptor gene required about 2.5 times higher concentration of NaCl solution to detect salty taste compared to those with CC genotype. Moreover, the incidence of hypertension assessed by ambulatory blood pressure measurements (⬎140/90 mmHg) was significantly (p⫽0.017) higher in elderly subjects with the AA genotype (63%) than those with AC or CC genotypes (30%) (chi-square). On the other hand, there was significant (p⫽0.005) correlation (Spearman) between the salty taste threshold and decrease in diastolic blood pressure from the value at ambulatory measurement to that after restriction of salt intake (7 g/day) for 4 weeks. These observations indicate participation of AT2 receptor gene polymorphism in salty taste disturbance and in salt-sensitive increase in blood pressure in elderly patients with hypertension. Key Words: polymorphism, Salty taste disturbance, AT2 receptor
P-150 POLYMORPHISMS IN MTHFR, ACE AND AGT GENES IN HYPERTENSIVE PATIENTS WITH PREMATURE ATHEROSCLEROSIS Pavel J. Levy, Carla Yunis, John Owen, Ronald D. Smith, Carlos M. Ferrario. 1Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States Younger adults with multiple cardiovascular risk factors (CVRF) are at greater risk for premature peripheral atherosclerosis (PASO). We conducted a prospective evaluation of the association between hypertension and the 677C3 T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, the I/D polymorphism in angiotensin converting enzyme (ACE) gene, and the A/G polymorphism in the angiotensinogen (AGT) gene in 92 patients (43% females, 84% white) ⱕ 55 years of age (mean 45 yrs) with severe PASO. Forty-three hypertensive patients (44% females; Group A) were compared to 49 normotensive subjects (43% females; Group B). Patients in both groups had similar profile of CVRF, however Group A subjects had higher frequencies of dyslipidemia (79%
MTHFR
ACE/DI
ACE/DD
AGT/AG
AGT/GG
AGT/AA
23(53) 24(49)
23(58) 26(53)
13(30) 19(39)
13/40(33)* 30/44(68)
15(38)* 6(14)
12(28) 8(18)
* P⬍0.05
MTHFR mutation was more prevalent in subjects with sys-ASO in both groups (P⫽0.004). Hypertensive patients with sys-ASO (n⫽32) had greater frequency of AGT/GG when compared to normotensive individuals with sys-ASO (n⫽29) (37% vs 10% respectively, P⬍0.05). Conclusion: Hypertensive patients with premature peripheral atherosclerotic disease had significantly greater frequency of systemic atherosclerosis. AGT/GG genotype was specifically associated with hypertension in these patients. Grant/Research Support: Bristol-Myers, Squibb Speakers’ Bureau: Sanofi; BMS; Aventis Key Words: Hypertension, Peripheral Atherosclerosis, Genotyping
P-151 ASSOCIATION STUDY OF 7 CANDIDATE GENES WITH ESSENTIAL HYPERTENSION IN SUBJECTS OF AFRICAN ANCESTRY Geoffrey P. Candy, A. J. Woodiwiss, A. Tiago, D. Deftereos, R. Brooksbank, D. Badenhorst, I. V. Radevski, N. J. Samani, P. Sareli, G. R. Norton. 1Cardiovascular pathophysiology, Physiology, University of the Witwatersrand, Johannesburg, South Africa, 2Cardiology and Nuclear Cardiology, Chris Hani-Baragwanath Hospital, Johanesburg, South Africa, 3Cardiology, University of Leicester, Leicester, United Kingdom Although a number of gene variants of the enzymes and substrates that influence either the production of vasoactive substances or that control body fluid balance, have been shown to be associated with hypertension, these data have not been confirmed in all population groups. Genotyping for 7 candidate genes (see Table) was performed in black South African hypertensive patients (mean daytime ambulatory DBP⬎ 90mm Hg) and healthy control subjects (office DBP⬍90mm Hg). Table. Candidate gene polymorphisms and their association with hypertension. *p⬍0.005 Candidate gene (1) (risk allele)
n Case/n Control
Odds Ratio (95% CI)
ACE (D) ATG (235T) ATG (-6A) ATG (-20C) CYP11B2 (C-344) eNOS (Glu298) Gi (C825) Gs (C131) eNa⫹ (594M)
551/538 554/539 196/124 545/576 547/549 503/511 478/602 504/588 514/513
0.85(0.71-1.01) 1.13(0.88-1.46) 1.19(0.65-2.16) 1.00(0.78-1.28) 1.05(0.85-1.31) 0.97(0.71-1.33) 1.49(1.17-1.89)* 1.40(1.10-1.78)* 1.05(0.57-1.92)
1ACE: angiotensin converting enzyme; ATG: angiotensinogen; CYP11B2: aldosterone synthase; eNOS: nitric oxide synthase; Gi: inhibitory G protein; Gs stimulatory G protein; eNa⫹: sodium epithelial channel The G protein gene polymorphisms, but not the other candidate gene polymorphisms investigated, are independently associated with hypertension in black South Africans. Key Words: hypertension
POSTERS: Genetics/Gene Therapy
Conclusion: The increase of non-dipper in the carrier of CC genotype was one of the reasons suggesting the genetic involvement of AGT polymorphism in the risk for cardiovascular disease.
AJH–April 2001–VOL. 14, NO. 4, PART 2
vs 57%, P⫽0.03), familial premature CV disease (65% vs 39%, P⫽0.02) and clinical systemic atherosclerosis [sys-ASO; ⬎ 1 anatomic location] (74% vs 41% P⫽0.002). The Table below summarizes the genetic profile of the subjects.
Key Words: angiotensinogen gene, 24hr blood pressure, genetic analysis Group A Group B
P-149 ANGIOTENSIN II TYPE2 (AT2) RECEPTOR GENE POLYMORPHISM AND HYPERTENSION IN THE ELDERLY WITH SALTY TASTE DISTURBANCE Shoroku Sakurai, Kohya Okaishi, Shigeto Morimoto. 1Department of Geriatric Medicine, Osaka University Medical School, Yamadaoka, Suita, Osaka, Japan Although hypertension in the elderly is highly dependent on excess intake of sodium, at least partially based on salty taste disturbance, little is known about association of gene polymorphisms with hypertension in the elderly with salty taste disturbance. To clarify the role of gene polymorphisms in this mechanism, 126 elderly female subjects and 61 male subjects were enrolled (mean age ⫹ SD; 81 ⫹ 7 years) for determination of magnitudes of NaCl (1.25%, 2.5%, 5%, 10% and 20%) in aqueous solution. Thresholds for salty taste were divided into six grades. Non of the subjects took angiotensin-I converting enzyme (ACE) inhibitors or angiotensin II type 1 (AT1) receptor antagonists. We analyzed A1166C polymorphism of human AT1 receptor gene, C3123A polymorphism of AT2 receptor gene mapped on human X chromosome, angiotensinogen M235T polymorphism, and angiotensin-I converting enzyme gene I/D polymorphism. There was a significant (female; p⫽0.005,male;p⫽0.040) association (ANOVA) of salty taste threshold with the AT2 receptor gene polymorphism, but not with other polymorphisms. Thus the elderly subject with AA genotype of the AT2 receptor gene required about 2.5 times higher concentration of NaCl solution to detect salty taste compared to those with CC genotype. Moreover, the incidence of hypertension assessed by ambulatory blood pressure measurements (⬎140/90 mmHg) was significantly (p⫽0.017) higher in elderly subjects with the AA genotype (63%) than those with AC or CC genotypes (30%) (chi-square). On the other hand, there was significant (p⫽0.005) correlation (Spearman) between the salty taste threshold and decrease in diastolic blood pressure from the value at ambulatory measurement to that after restriction of salt intake (7 g/day) for 4 weeks. These observations indicate participation of AT2 receptor gene polymorphism in salty taste disturbance and in salt-sensitive increase in blood pressure in elderly patients with hypertension. Key Words: polymorphism, Salty taste disturbance, AT2 receptor
P-150 POLYMORPHISMS IN MTHFR, ACE AND AGT GENES IN HYPERTENSIVE PATIENTS WITH PREMATURE ATHEROSCLEROSIS Pavel J. Levy, Carla Yunis, John Owen, Ronald D. Smith, Carlos M. Ferrario. 1Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States Younger adults with multiple cardiovascular risk factors (CVRF) are at greater risk for premature peripheral atherosclerosis (PASO). We conducted a prospective evaluation of the association between hypertension and the 677C3 T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, the I/D polymorphism in angiotensin converting enzyme (ACE) gene, and the A/G polymorphism in the angiotensinogen (AGT) gene in 92 patients (43% females, 84% white) ⱕ 55 years of age (mean 45 yrs) with severe PASO. Forty-three hypertensive patients (44% females; Group A) were compared to 49 normotensive subjects (43% females; Group B). Patients in both groups had similar profile of CVRF, however Group A subjects had higher frequencies of dyslipidemia (79%
MTHFR
ACE/DI
ACE/DD
AGT/AG
AGT/GG
AGT/AA
23(53) 24(49)
23(58) 26(53)
13(30) 19(39)
13/40(33)* 30/44(68)
15(38)* 6(14)
12(28) 8(18)
* P⬍0.05
MTHFR mutation was more prevalent in subjects with sys-ASO in both groups (P⫽0.004). Hypertensive patients with sys-ASO (n⫽32) had greater frequency of AGT/GG when compared to normotensive individuals with sys-ASO (n⫽29) (37% vs 10% respectively, P⬍0.05). Conclusion: Hypertensive patients with premature peripheral atherosclerotic disease had significantly greater frequency of systemic atherosclerosis. AGT/GG genotype was specifically associated with hypertension in these patients. Grant/Research Support: Bristol-Myers, Squibb Speakers’ Bureau: Sanofi; BMS; Aventis Key Words: Hypertension, Peripheral Atherosclerosis, Genotyping
P-151 ASSOCIATION STUDY OF 7 CANDIDATE GENES WITH ESSENTIAL HYPERTENSION IN SUBJECTS OF AFRICAN ANCESTRY Geoffrey P. Candy, A. J. Woodiwiss, A. Tiago, D. Deftereos, R. Brooksbank, D. Badenhorst, I. V. Radevski, N. J. Samani, P. Sareli, G. R. Norton. 1Cardiovascular pathophysiology, Physiology, University of the Witwatersrand, Johannesburg, South Africa, 2Cardiology and Nuclear Cardiology, Chris Hani-Baragwanath Hospital, Johanesburg, South Africa, 3Cardiology, University of Leicester, Leicester, United Kingdom Although a number of gene variants of the enzymes and substrates that influence either the production of vasoactive substances or that control body fluid balance, have been shown to be associated with hypertension, these data have not been confirmed in all population groups. Genotyping for 7 candidate genes (see Table) was performed in black South African hypertensive patients (mean daytime ambulatory DBP⬎ 90mm Hg) and healthy control subjects (office DBP⬍90mm Hg). Table. Candidate gene polymorphisms and their association with hypertension. *p⬍0.005 Candidate gene (1) (risk allele)
n Case/n Control
Odds Ratio (95% CI)
ACE (D) ATG (235T) ATG (-6A) ATG (-20C) CYP11B2 (C-344) eNOS (Glu298) Gi (C825) Gs (C131) eNa⫹ (594M)
551/538 554/539 196/124 545/576 547/549 503/511 478/602 504/588 514/513
0.85(0.71-1.01) 1.13(0.88-1.46) 1.19(0.65-2.16) 1.00(0.78-1.28) 1.05(0.85-1.31) 0.97(0.71-1.33) 1.49(1.17-1.89)* 1.40(1.10-1.78)* 1.05(0.57-1.92)
1ACE: angiotensin converting enzyme; ATG: angiotensinogen; CYP11B2: aldosterone synthase; eNOS: nitric oxide synthase; Gi: inhibitory G protein; Gs stimulatory G protein; eNa⫹: sodium epithelial channel The G protein gene polymorphisms, but not the other candidate gene polymorphisms investigated, are independently associated with hypertension in black South Africans. Key Words: hypertension