Genetic Analysis of Candidate Gene Polymorphisms in Elderly Hypertension
Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only...
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| Published in | Nihon Rōnen Igakkai zasshi Vol. 36; no. 8; pp. 547 - 552 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
Japan
The Japan Geriatrics Society
1999
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0300-9173 |
| DOI | 10.3143/geriatrics.36.547 |
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| Abstract | Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (<60) and elderly (≥60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging. |
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| AbstractList | Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (<60) and elderly (≥60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging. Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (< 60) and elderly (> or = 60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging. Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (< 60) and elderly (> or = 60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging.Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (< 60) and elderly (> or = 60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging. |
| Author | Ogihara, Toshio Sato, Noriyuki Ishikawa, Kazuhiko Higaki, Jitsuo Katsuya, Tomohiro |
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| References | 1) Kamitani A, Rakugi H, Higaki J, Yi Z, Mikami H, Miki T, et al.: Association analysis of a polymorphism of the angiotensinogen gene with essential hypertension in Japanese. J Hum Hypertens 1994; 8: 521-524. 2) Ohishi M, Rakugi H, and Ogihara T: Association between a deletion polymorphism of the angiotensinconverting-enzyme gene and left ventricular hypertrophy. N Engl J Med 1994; 331: 1097-1098. 4) Katsuya T, Horiuchi M, Minami S, Koike G, Santoro NF, Hsueh AJ, et al.: 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. 11) Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, et al.: A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 1995; 332: 706-711. 7) Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, et al.: Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993; 43: 1467-1472. 13) Ishikawa K, Katsuya T, Sato N, Nakata Y, Takami S, Takiuchi S, et al.: No association between alpha-adducin 460 polymorphism and essential hypertension in Japanese population. Am J Hypertens 1998; 11: 502-506. 15) O'Donnell CJ, Lindpaintner K, Larson MG, Rao VS, Ordovas JM, Schaefer EJ, et al.: 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 1998; 97: 1766-1772. 9) Russ AP, Maerz W, Ruzicka V, Stein U, and Gross W: Rapid detection of the hypertension-associated Met235 →Thr allele of the human angiotensinogen gene. Hum Mol Genet 1993; 2: 609-610. 6) Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al.: A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-113. 16) Fornage M, Amos CI, Kardia S, Sing CF, Turner ST, and Boerwinkle E: Variation in the region of the angiotensinconverting enzyme gene influences interindividual differences in blood pressure levels in young white males. Circulation 1998; 97: 1773-1779. 3) Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charru A, Clauser E, et al.: Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 1994; 24: 63-69. 12) Takami S, Katsuya T, Rakugi H, Sato N, Nakata Y, Kamitani A, et al.: Angiotensin II type 1 receptor gene polymorphism is associated with increase of left ventricular mass but not with hypertension. Am J Hypertens 1998; 11: 316-321. 18) Takemoto Y, Sakatani M, Takami S, Tachibana T, Higaki J, Ogihara T, et al.: Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACS) activity in patients with sarcoidosis. Thorax 1998; 53: 459-462. 8) Bullido MJ, Artiga MJ, Recuero M, Sastre I, Garcia MA, Aldudo J, et al.: A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia. Nat Genet 1998; 18: 69-71. 5) Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M, et al.: Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Lancet 1997; 349: 1353-1357. 10) Rigat B, Hubert C, Corvol P, and Soubrier F: PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 1992; 20: 1433. 14) Nakata Y, Katsuya T, Takami S, Sato N, Fu Y, Ishikawa K, et al.: Methylenetetrahydrofolate reductase gene polymorphism: relation to blood pressure and cerebrovascular disease. Am J Hypertens 1998; 11: 1019-1023. 17) Hein L, Dzau VJ, and Barsh GS: Linkage mapping of the angiotensin AT2 receptor gene (Agtr2) to the mouse X chromosome. Genomics 1995; 30: 369-371. 19) Haywood GA, Gullestad L, Katsuya T, Hutchinson HG, Pratt RE, Horiuchi M, et al.: AT1 and AT2 angiotensin receptor gene expression in human heart failure. Circulation 1997; 95: 1201-1206. |
| References_xml | – reference: 15) O'Donnell CJ, Lindpaintner K, Larson MG, Rao VS, Ordovas JM, Schaefer EJ, et al.: 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 1998; 97: 1766-1772. – reference: 6) Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al.: A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-113. – reference: 4) Katsuya T, Horiuchi M, Minami S, Koike G, Santoro NF, Hsueh AJ, et al.: 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. – reference: 7) Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, et al.: Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993; 43: 1467-1472. – reference: 17) Hein L, Dzau VJ, and Barsh GS: Linkage mapping of the angiotensin AT2 receptor gene (Agtr2) to the mouse X chromosome. Genomics 1995; 30: 369-371. – reference: 2) Ohishi M, Rakugi H, and Ogihara T: Association between a deletion polymorphism of the angiotensinconverting-enzyme gene and left ventricular hypertrophy. N Engl J Med 1994; 331: 1097-1098. – reference: 1) Kamitani A, Rakugi H, Higaki J, Yi Z, Mikami H, Miki T, et al.: Association analysis of a polymorphism of the angiotensinogen gene with essential hypertension in Japanese. J Hum Hypertens 1994; 8: 521-524. – reference: 8) Bullido MJ, Artiga MJ, Recuero M, Sastre I, Garcia MA, Aldudo J, et al.: A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia. Nat Genet 1998; 18: 69-71. – reference: 13) Ishikawa K, Katsuya T, Sato N, Nakata Y, Takami S, Takiuchi S, et al.: No association between alpha-adducin 460 polymorphism and essential hypertension in Japanese population. Am J Hypertens 1998; 11: 502-506. – reference: 5) Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M, et al.: Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Lancet 1997; 349: 1353-1357. – reference: 9) Russ AP, Maerz W, Ruzicka V, Stein U, and Gross W: Rapid detection of the hypertension-associated Met235 →Thr allele of the human angiotensinogen gene. Hum Mol Genet 1993; 2: 609-610. – reference: 12) Takami S, Katsuya T, Rakugi H, Sato N, Nakata Y, Kamitani A, et al.: Angiotensin II type 1 receptor gene polymorphism is associated with increase of left ventricular mass but not with hypertension. Am J Hypertens 1998; 11: 316-321. – reference: 10) Rigat B, Hubert C, Corvol P, and Soubrier F: PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 1992; 20: 1433. – reference: 19) Haywood GA, Gullestad L, Katsuya T, Hutchinson HG, Pratt RE, Horiuchi M, et al.: AT1 and AT2 angiotensin receptor gene expression in human heart failure. Circulation 1997; 95: 1201-1206. – reference: 16) Fornage M, Amos CI, Kardia S, Sing CF, Turner ST, and Boerwinkle E: Variation in the region of the angiotensinconverting enzyme gene influences interindividual differences in blood pressure levels in young white males. Circulation 1998; 97: 1773-1779. – reference: 3) Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charru A, Clauser E, et al.: Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 1994; 24: 63-69. – reference: 14) Nakata Y, Katsuya T, Takami S, Sato N, Fu Y, Ishikawa K, et al.: Methylenetetrahydrofolate reductase gene polymorphism: relation to blood pressure and cerebrovascular disease. Am J Hypertens 1998; 11: 1019-1023. – reference: 18) Takemoto Y, Sakatani M, Takami S, Tachibana T, Higaki J, Ogihara T, et al.: Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACS) activity in patients with sarcoidosis. Thorax 1998; 53: 459-462. – reference: 11) Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, et al.: A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 1995; 332: 706-711. |
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| SubjectTerms | Aged Aging, Genetics Angiotensin II - genetics Angiotensinogen - genetics Apolipoproteins - genetics Case control study Case-Control Studies Female Genetic predisposing factor Humans Hypertension - genetics Male Middle Aged Peptidyl-Dipeptidase A - genetics Polymorphism, Genetic Renin angiotensin system Risk Factors |
| Title | Genetic Analysis of Candidate Gene Polymorphisms in Elderly Hypertension |
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