Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Blood Pressure in Relation to α-Adducin, Angiotensinogen, ACE Gene Polymorphisms and Sodium Intake in Korean Female Elderly Subjects

한국 여성 노인에서 α -Adducin, Angiotensinogen, ACE 유전자다형성 및 나트륨 섭취수준에 따른 혈압의 비교

  • 채선주 (경희대학교 생활과학대학 식품영양학과) ;
  • 정자용 (경희대학교 생활과학대학 식품영양학과)
  • Published : 2006.12.29
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Abstract

Gene polymorphisms that are associated with sodium homeostasis in the body, such as $\alpha-adducin$ (ADDI, Gly460Trp), angiotensinogen (AGT, Met235Thr), and angiotensin converting enzyme (ACE, Ins/Del) may increase the risk for the development of hypertension. The purpose of this study was to elucidate the relationship between the singular and combined effects of ADD1, AGT, ACE genotypes, and blood pressure in elderly population. Moreover, we examined the interaction of sodium intake and polymorphisms of aforementioned genes and their effects on blood pressure. Among one hundred and nine female subjects, aged 60 and over (mean 75.9 yr), the major alleles for ADD1, AGT, and ACE polymorphisms in the studied population were Gly (66.1%), Thr (64.2%), Ins (83.5%), respectively. Analysis on the combined effects of genetic variation showed that subjects who were both ADD1 Trp/Trp and ACE Del/Del homozygotes had significantly higher systolic blood pressure (p=0.01). Similarly, ACE Del/Del homozygotes who had AGT Met allele had significantly higher diastolic blood pressure (p<0.001). However, in single-gene analyses, no association was found between any specific genotype and blood pressure. In subjects with low sodium intake, ADD1 Trp/Trp homozygotes had significantly higher systolic blood pressure than subjects who had ADD1 Gly allele (138 mmHg vs. 127 mmHg, p=0.03). There was no difference in blood pressure between ADD1 Trp/Trp and ADD1 Gly/Gly or Gly/Trp, in subjects with high sodium intake. In summary, this study shows that interactions between the ADD1, AGT and ACE genes influence systolic and diastolic blood pressure in elderly subjects, and dietary sodium intake can modulate the effects of ADD1 Gly460Trp polymorphisms on systolic blood pres sure.

본 연구에서는 60대 이상 한국 여성 노인을 대상으로 하여 체내 나트륨 대사에 밀접하게 관여하는 ADD1 Gly460Trp, AGT Met235Thr, ACE Ins/Del 유전자형의 분포를 살피고 각각의 유전자 다형성 혹은 유전자형의 조합과 수축기 및 이완기 혈압과의 관계, 그리고 식이 나트륨 섭취 수준이 유전자-혈압과의 관계에 미치는 영향에 대해 파악하고자 수행 되었으며 그 결과를 요약하면 다음과 같다. 본 연구에서 분석된 유전자형들의 분포는 1) ADD1 유전자-Gly/Gly:Gly/Trp:Trp/Trp=16.5:49.5:34.0, 2) AGT 유전자-Met/Met:Met/Thr:Thr/Thr=4.6:31.2:64.2, 3) ACE 유전자-Ins/Ins:Ins/Del:Del/Del=34:49.5:16.5이었다. AAD1 Gly460Trp, AGT Met235Thr, ACE Ins/Del 각각의 유전자형은 본 연구대상자들의 수축기 및 이완기 혈압을 유의하게 변화시키지 않았으나, ACE Del/Del형과 ADD1 Trp/Trp형을 동시에 보유하고 있는 경우 다른 유전자형을 가진 대상자들에 비해 수축기 혈압이 유의적으로 높았으며(p=0.01), ACE Del/Del형과 AGT Met allele을 동시 에 보유하고 있는 경우 다른 그룹들에 비해 높은 이완기 혈압을 가지고 있는 것으로 나타났다(p<0.001).식이 나트륨 섭취량의 상대적인 수준에 따라 전체 대상자를 두 그룹으로 나누었을 때, 나트륨 섭취량이 낮은 그룹에서만 ADD1 Gly460Trp유전자형에 따른 평균 수축기 혈압의 차이가 관찰되었고(p=0.03), 나트륨 섭취량이 높은 그룹에서는 ADD1유전자형별 평균 수축기 및 이완기 혈압에 유의적인 차이가 없었다. 이상의 결과는 한국 여성 노인에 있어 혈압의 증가에 ADD1, AGT 및 ACE유전자 다형성이 복합적으로 관여함을 제시한다. 또한, 이들 유전자 다형성에 대한 혈압의 표현형이 식이 나트륨 섭취 수준에 따라 변화함을 규명하였다. 이러한 결과로 볼 때, 앞으로 유전자-질병간의 연관성을 밝히기 위한 연구들에서 단일 유전자보다는 다양한 유전자들에 대한 분석이 복합적으로 이루어져야 하며, 식이 요인 등 주요 환경 요인에 대한 분석이 반드시 함께 수행되어야 할 것으로 생각된다.

Keywords

References

  1. Korea National Statistical Office. 2006. The causes of death statistics in 2005
  2. Stamler J. 1993. Dietary salt and blood pressure. Ann N Y Acad Sci 676: 122-156 https://doi.org/10.1111/j.1749-6632.1993.tb38730.x
  3. Klag MJ, Whelton PK, Randall BL Neaton JD, Brancaei FL, Stamler J. 1997. End-stage renal disease in African- American and white men. 16-year MRFIT findings. JAMA 277: 1293-1298 https://doi.org/10.1001/jama.277.16.1293
  4. Cook NR, Cohen J, Hebert PR, Taylor JO, Hennekens CH. 1995. Implications of small reductions in diastolic blood pressure for primary prevention. Arch Intern Med 155:701-709 https://doi.org/10.1001/archinte.155.7.701
  5. The National High Blood Pressure Education Program Coordinating Committee. 2003. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 289: 2560-2572 https://doi.org/10.1001/jama.289.19.2560
  6. Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M, Glorioso N, Lanzani C, Manunta P, Righetti M, Rivera R, Stella P, Troffa C, Zagato L. 1997. Polymorphisms of alpha-ADD1 and salt sensitivity in patients with essential hypertension. Lancet 349: 1353-1357 https://doi.org/10.1016/S0140-6736(97)01029-5
  7. Manunta P, Cusi D, Barlassina C, Righetti M, Lanzani C, D'Amico M, Buzzi L, Citterio L, Stella P, Rivera R, Bianchi G. 1998. Alpha-ADD1 polymorphisms and renal sodium handling in essential hypertensive patients. Kidney Int 53: 1471-1478 https://doi.org/10.1046/j.1523-1755.1998.00931.x
  8. Glorioso N, Manunta P, Filigheddu F, Troffa C, Stella P, Barlassina C, Lombardi C, Soro A, Dettori F, Parpaglia PP, Alibrandi MT, Cusi D, Bianchi G. 1999. The role of alpha-ADD1 polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study. Hypertension 34: 649-654 https://doi.org/10.1161/01.HYP.34.4.649
  9. Grant FD, Romero JR, Jeunemaitre X, Hunt SC, Hopkins PN, Hollenberg NH, Williams GH. 2002. Low-renin hypertension, altered sodium homeostasis, and an alpha-ADD1 polymorphism. Hypertension 39: 191-196 https://doi.org/10.1161/hy0202.104273
  10. Hall JE, Granger JP. 1982. Mechanism of the blood pressure and renal hemodynamic effects of captopril. Am J Cardiol 49: 1527-1529 https://doi.org/10.1016/0002-9149(82)90377-0
  11. Jeunemaitre X, Lifton RP, Hunt SC, Williams RR, Lalouel JM. 1992. Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension. Nat Genet 1: 72-75 https://doi.org/10.1038/ng0492-72
  12. Jeunemaitre X, Inoue I, Williams C, Charru A, Tichet J, Powers M, Sharma AM, Gimenez-Roqueplo AP, Hata A, Corvol P, Lalouel JM. 1997. Haplotypes of angiotensinogen in essential hypertension. Am J Hum Genet 60: 1448-1460 https://doi.org/10.1086/515452
  13. Hata A, Namikawa C, Sasaki M, Sato K, Nakamura T, Tamura K, Lalouel JM. 1994. Angiotensinogen as a risk factor for essential hypertension in Japan. J Clin Invest 93: 1285-1287 https://doi.org/10.1172/JCI117083
  14. Bloem LJ, Manatunga AK, Tewksbury DA, Pratt JH. 1995. The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children. J Clin Invest 95: 948-953 https://doi.org/10.1172/JCI117803
  15. Iwai N, Shimoike H, Ohmichi N, Kinoshita M. 1995. Angiotensinogen gene and blood pressure in the Japanese population. Hypertension 25: 688-693 https://doi.org/10.1161/01.HYP.25.4.688
  16. Borecki IB, Province MA, Ludwig EH, Ellison RC, Folsom AR, Heiss G, Lalouel JM, Higgins M, Rao DC. 1997. Associations of candidate loci angiotensinogen and angiotensin-converting enzyme with severe hypertension: The NHLBI Family Heart Study. Ann Epidemiol 7: 13-21 https://doi.org/10.1016/S1047-2797(97)00155-5
  17. Schunkert H, Hense HW, Gimenez-Roqueplo AP, Stieber J, Keil U, Riegger GA, Jeunemaitre X. 1997. The angiotensinogen T235 variant and the use of antihypertensive drugs in a population-based cohort. Hypertension 29: 628-633 https://doi.org/10.1161/01.HYP.29.2.628
  18. Kunz R, Kreutz R, Beige J, Distler A, Sharma AM. 1997. Association between the angiotensinogen 235T-variant and essential hypertension in whites: a systematic review and methodological appraisal. Hypertension 30: 1331-1337 https://doi.org/10.1161/01.HYP.30.6.1331
  19. Staessen JA, Kuznetsova T, Wang JG, Emelianov D, Vlietinck R, Fagard R. 1999. M235T angiotensinogen gene polymorphism and cardiovascular renal risk. J Hypertens 17: 9-17 https://doi.org/10.1097/00004872-199917010-00003
  20. Hegele RA, Brunt JH, Connelly PW. 1994. A polymorphism of the angiotensinogen gene associated with variation in blood pressure in a genetic isolate. Circulation 90: 2207- 2212 https://doi.org/10.1161/01.CIR.90.5.2207
  21. Rotimi C, Morrison L, Cooper R, Oyejide C, Effiong E, Ladipo M, Osotemihen B, Ward R. 1994. Angiotensinogen gene in human hypertension. Lack of an association of the 235T allele among African Americans. Hypertension 24: 591-594 https://doi.org/10.1161/01.HYP.24.5.591
  22. Fornage M, Turner ST, Sing CF, Boerwinkle E. 1995. Variation at the M235T locus of the angiotensinogen gene and essential hypertension: a population-based case-control study from Rochester, Minnesota. Hum Genet 96: 295-300
  23. Forrester T, McFarlane-Anderson N, Bennet F, Wilks R, Puras A, Cooper R, Rotimi C, Durazo R, Tewksbury D, Morrison L. 1996. Angiotensinogen and blood pressure among blacks: findings from a community survey in Jamaica. J Hypertens 14: 315-321 https://doi.org/10.1097/00004872-199603000-00007
  24. Hingorani AD, Sharma P, Jia H, Hopper R, Brown MJ. 1996. Blood pressure and the M235T polymorphism of the angiotensinogen gene. Hypertension 28: 907-911 https://doi.org/10.1161/01.HYP.28.5.907
  25. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. 1990. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86: 1343-1346 https://doi.org/10.1172/JCI114844
  26. O'Donnell CJ, Lindpaintner K, Larson MG, Rao VS, Ordovas JM, Schaefer EJ, Myers RH, Levy D. 1998. Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation 97: 1766-1772 https://doi.org/10.1161/01.CIR.97.18.1766
  27. Fornage M, Amos CI, Kardia S, Sing CF, Turner ST, Boerwinkle E. 1998. Variation in the region of the angiotensin-converting enzyme gene influences interindividual differences in blood pressure levels in young white males. Circulation 97: 1773-1779 https://doi.org/10.1161/01.CIR.97.18.1773
  28. Uemura K, Nakura J, Kohara K, Miki T. 2000. Association of ACE I/D polymorphism with cardiovascular risk factors. Hum Genet 107: 239-242 https://doi.org/10.1007/s004390000358
  29. Henskens LH, Spiering W, Stoffers HE, Soomers FL, Vlietinck RF, de Leeuw PW, Kroon AA. 2003. Effects of ACE I/D and AT1R-A1166C polymorphisms on blood pressure in a healthy normotensive primary care population: first results of the Hippocates study. J Hypertens 21: 81-86 https://doi.org/10.1097/00004872-200301000-00017
  30. Kiema TR, Kauma H, Rantala AO, Lilja M, Reunanen A, Kesaniemi YA, Savolainen MJ. 1996. Variation at the angiotensin-converting enzyme gene and angiotensinogen gene loci in relation to blood pressure. Hypertension 28: 1070-1075 https://doi.org/10.1161/01.HYP.28.6.1070
  31. Kiema TR, Kauma H, Rantala AO, Lilja M, Reunanen A, Kesaniemi YA, Savolainen MJ. 1996. Variation at the angiotensin-converting enzyme gene and angiotensinogen gene loci in relation to blood pressure. Hypertension 28: 1070-1075 https://doi.org/10.1161/01.HYP.28.6.1070
  32. Kim HJ, Paik HY, Lee SY, Shim JE, Kim YS. 2007. Salt usage behaviors are related to urinary sodium excretion in normotensive Korean adults. Asia Pac J Clin Nutr in press
  33. International Obesity Task Force. 1999. Reassessment of anthropometric indices of obesity. Asian BMI/obesity workshop meeting, Milano, Italy
  34. Berge KE, Berg K. 1998. Polymophism at the AGT and angiotensin II type 1 receptor loci and normal blood pressure. Clin Genet 53: 214-219 https://doi.org/10.1111/j.1399-0004.1998.tb02680.x
  35. Wang JG, Liu L, Zagato L, Xie J, Fagard R, Jin K, Wang J, Li Y, Bianchi G, Staessen JA, Liu L. 2004. Blood pressure in relation to three candidate genes in a Chinese population. J Hypertens 22: 937-944 https://doi.org/10.1097/00004872-200405000-00015
  36. Staessen JA, Wang JG, Brand E, Barlassina C, Birkenhager WH, Herrmann SM, Fagard R, Tizzoni L, Bianchi G. 2001 Effects of three candidate genes on prevalence and incidence of hypertension in a Caucasian population. J Hypertens 19: 1349-1358 https://doi.org/10.1097/00004872-200108000-00002
  37. Yamagishi K, Iso H, Tanigawa T, Cui R, Kudo M, Shimamoto T. 2004. Alpha-ADD1 G460W polymorphism, urinary sodium excretion, and blood pressure in community-based samples. Am J Hypertens 17: 385-390 https://doi.org/10.1016/j.amjhyper.2003.12.018