Nutr Res Pract.  2015 Aug;9(4):385-392. 10.4162/nrp.2015.9.4.385.

Lifestyle intervention might easily improve blood pressure in hypertensive men with the C genotype of angiotensin II type 2 receptor gene

• Kitaoka K
• Kitade A
• Nagaoka J
• Tsuzaki K
• Harada K
• Aoi W
• Wada S
• Asano H
• Sakane N
• Higashi A

• KMID: 2313855
• DOI: http://doi.org/10.4162/nrp.2015.9.4.385

Abstract

BACKGROUND/OBJECTIVES
Recent studies have reported an association of the angiotensin II type 2 receptor (AT2R) 3123Cytosine/Adenine (3123C/A) polymorphism with essential hypertension and cardiovascular diseases. The purpose of the study was to investigate whether the AT2R 3123C/A polymorphism affects blood pressure for free-living hypertensive men during a 5-month intervention period.
SUBJECTS/METHODS
The subjects were free-living hypertensive Japanese men aged 40 to 75 years who agreed to intervention in the period from 2004 to 2011. Detection of the AT2R 3123C/A polymorphism was determined by polymerase chain reaction. The dietary intervention was designed to decrease salt level and to increase potassium level through cooking instructions and self-monitoring of the diet. The exercise session consisted of activities such as stretching, resistance training, and walking. Blood pressure, urinary sodium and potassium excretion, dietary and lifestyle data, and non-fasting venous blood sample were collected at baseline and after the intervention period.
RESULTS
Thirty nine subjects were eligible for participation and the follow-up rate was 97.4%. The C allele proportion was 57.9%. AT2R 3123C/A polymorphism was X-chromosome-linked, therefore we analyzed the C and A genotypes. At baseline, no significant differences were observed between the genotype groups. After the intervention, there were no significant differences in lifestyle habit between the groups. Nevertheless, the estimated salt excretion (g/day) was significantly decreased only in the C genotype (13.0-10.3, P = 0.031). No significant change was observed in systolic blood pressure (SBP) (mmHg) in the A genotype, but a significant decrease was observed in the C genotype (150.0-141.5, P = 0.024). CONCLUSTIONS: In the C genotype, it might be easy to improve SBP through lifestyle intervention in free-living hypertensive Japanese men, however generalization could not be achieved by the small sample size.

Keyword

AT2R gene; blood pressure; salt excretion; lifestyle modification; hypertensive men

MeSH Terms

Alleles
Asian Continental Ancestry Group
Blood Pressure*
Cardiovascular Diseases
Cooking
Diet
Follow-Up Studies
Generalization (Psychology)
Genotype*
Humans
Hypertension
Life Style*
Male
Polymerase Chain Reaction
Potassium
Receptor, Angiotensin, Type 2*
Resistance Training
Sample Size
Sodium
Walking
Potassium
Receptor, Angiotensin, Type 2
Sodium

Reference

1. Kato N. Genetic analysis in human hypertension. Hypertens Res. 2002; 25:319–327.

2. Cook NR, Obarzanek E, Cutler JA, Buring JE, Rexrode KM, Kumanyika SK, Appel LJ, Whelton PK. Trials of Hypertension Prevention Collaborative Research Group. Joint effects of sodium and potassium intake on subsequent cardiovascular disease: the Trials of Hypertension Prevention follow-up study. Arch Intern Med. 2009; 169:32–40.

3. Kannel WB, Dawber TR, McGee DL. Perspectives on systolic hypertension. The Framingham study. Circulation. 1980; 61:1179–1182.

4. Sodium, potassium, body mass, alcohol and blood pressure: the INTERSALT Study. The INTERSALT Co-operative Research Group. J Hypertens Suppl. 1988; 6:S584–S586.

5. Stamler J, Elliott P, Dennis B, Dyer AR, Kesteloot H, Liu K, Ueshima H, Zhou BF. INTERMAP Research Group. INTERMAP: background, aims, design, methods, and descriptive statistics (nondietary). J Hum Hypertens. 2003; 17:591–608.

6. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH. DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001; 344:3–10.

7. Shay CM, Stamler J, Dyer AR, Brown IJ, Chan Q, Elliott P, Zhao L, Okuda N, Miura K, Daviglus ML, Van Horn L. Nutrient and food intakes of middle-aged adults at low risk of cardiovascular disease: the international study of macro-/micronutrients and blood pressure (INTERMAP). Eur J Nutr. 2012; 51:917–926.

8. Miura K, Okuda N, Turin TC, Takashima N, Nakagawa H, Nakamura K, Yoshita K, Okayama A, Ueshima H. NIPPON DATA80/90 Research Group. Dietary salt intake and blood pressure in a representative Japanese population: baseline analyses of NIPPON DATA80. J Epidemiol. 2010; 20:Suppl 3. S524–S530.

9. Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, Stevens VJ, Vollmer WM, Lin PH, Svetkey LP, Stedman SW, Young DR. Writing Group of the PREMIER Collaborative Research Group. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003; 289:2083–2093.

10. Iso H, Shimamoto T, Yokota K, Sankai T, Jacobs DR Jr, Komachi Y. Community-based education classes for hypertension control. A 1.5-year randomized controlled trial. Hypertension. 1996; 27:968–974.

11. Miura K, Myogadani H, Kadoya Y, Hayashi M, Motoya M, Kuzumaki M, Yoneda M, Mitsui T, Nishijo M, Morikawa Y, Nakanishi Y, Nakashima M, Nakagawa H. Effectiveness of lifestyle modification programs for control of blood pressure: a non-randomized controlled trial in Komatsu, Japan. Nihon Koshu Eisei Zasshi. 2006; 53:533–542.

12. Fujii H, Muto T, Haruyama Y, Nakade M, Kobayashi E, Ishisaki K, Yamasaki A. Community-based lifestyle modification of cardiovascular disease risks in middle-aged Japanese: a 27-month update. Tohoku J Exp Med. 2010; 220:307–318.

13. Takahashi Y, Sasaki S, Okubo S, Hayashi M, Tsugane S. Blood pressure change in a free-living population-based dietary modification study in Japan. J Hypertens. 2006; 24:451–458.

14. Kitaoka K, Nagaoka J, Matsuoka T, Shigemura C, Harada K, Aoi W, Wada S, Asano H, Sakane N, Higashi A. Dietary intervention with cooking instructions and self-monitoring of the diet in free-living hypertensive men. Clin Exp Hypertens. 2013; 35:120–127.

15. Parfrey PS, Markandu ND, Roulston JE, Jones BE, Jones JC, MacGregor GA. Relation between arterial pressure, dietary sodium intake, and renin system in essential hypertension. Br Med J (Clin Res Ed). 1981; 283:94–97.

16. Carey RM, Jin XH, Siragy HM. Role of the angiotensin AT2 receptor in blood pressure regulation and therapeutic implications. Am J Hypertens. 2001; 14:98S–102S.

17. Jin JJ, Nakura J, Wu Z, Yamamoto M, Abe M, Chen Y, Tabara Y, Yamamoto Y, Igase M, Bo X, Kohara K, Miki T. Association of angiotensin II type 2 receptor gene variant with hypertension. Hypertens Res. 2003; 26:547–552.

18. Jones A, Dhamrait SS, Payne JR, Hawe E, Li P, Toor IS, Luong L, Wootton PT, Miller GJ, Humphries SE, Montgomery HE. Genetic variants of angiotensin II receptors and cardiovascular risk in hypertension. Hypertension. 2003; 42:500–506.

19. Zhang Y, Zhang KX, Wang GL, Huang W, Zhu DL. Angiotensin II type 2 receptor gene polymorphisms and essential hypertension. Acta Pharmacol Sin. 2003; 24:1089–1093.

20. Kokubo Y, Kamide K, Okamura T, Watanabe M, Higashiyama A, Kawanishi K, Okayama A, Kawano Y. Impact of high-normal blood pressure on the risk of cardiovascular disease in a Japanese urban cohort: the Suita study. Hypertension. 2008; 52:652–659.

21. Nakamura Y, Yamamoto T, Okamura T, Kadowaki T, Hayakawa T, Kita Y, Saitoh S, Okayama A, Ueshima H. NIPPON DATA 80 Research Group. Combined cardiovascular risk factors and outcome: NIPPON DATA80, 1980-1994. Circ J. 2006; 70:960–964.

22. Kawasaki T, Itoh K, Uezono K, Sasaki H. A simple method for estimating 24 h urinary sodium and potassium excretion from second morning voiding urine specimen in adults. Clin Exp Pharmacol Physiol. 1993; 20:7–14.

23. Ikeda J, Higashi A, Nagata H. Validity of scores calculated from the results of a food frequency questionnaire. Nihon Koshu Eisei Zasshi. 1995; 42:829–842.

24. Katsuya T, Horiuchi M, Minami S, Koike G, Santoro NF, Hsueh AJ, Dzau VJ. Genomic organization and polymorphism of human angiotensin II type 2 receptor: no evidence for its gene mutation in two families of human premature ovarian failure syndrome. Mol Cell Endocrinol. 1997; 127:221–228.

25. Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK. Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Nature. 1995; 377:744–747.

26. Ichiki T, Labosky PA, Shiota C, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan BL, Inagami T. Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature. 1995; 377:748–750.

27. Hamada T, Kotani K, Nagai N, Tsuzaki K, Sano Y, Matsuoka Y, Fujibayashi M, Kiyohara N, Tanaka S, Yoshimura M, Egawa K, Kitagawa Y, Kiso Y, Moritani T, Sakane N. Genetic polymorphisms of the renin-angiotensin system and obesity-related metabolic changes in response to low-energy diets in obese women. Nutrition. 2011; 27:34–39.

28. Luft FC, Weinberger MH. Heterogeneous responses to changes in dietary salt intake: the salt-sensitivity paradigm. Am J Clin Nutr. 1997; 65:612S–617S.

29. Ohkubo T, Imai Y, Tsuji I, Nagai K, Kato J, Kikuchi N, Nishiyama A, Aihara A, Sekino M, Kikuya M, Ito S, Satoh H, Hisamichi S. Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan. J Hypertens. 1998; 16:971–975.

30. Kawano Y, Tsuchihashi T, Matsuura H, Ando K, Fujita T, Ueshima H. Working Group for Dietary Salt Reduction of the Japanese Society of Hypertension. Report of the Working Group for Dietary Salt Reduction of the Japanese Society of Hypertension: (2) Assessment of salt intake in the management of hypertension. Hypertens Res. 2007; 30:887–893.