Abstract
Hypertension in pregnancy (HP) is a multifactorial disease manifested due to a complex combination of environmental factors and several predisposing genes including factors in the renin angiotensin system. The aim of this study was to assess the association between the A1166C variant of the angiotensin II type 1 receptor (AT1) gene and severe HP. We carried out association studies and multivariate analyses including other candidate causal factors of HP such as the M235T variant of the angiotensinogen (AGT) gene, prepregnancy body mass index (BMI), and family history of hypertension in Japanese subjects. One hundred and fourteen patients with severe HP and 291 normal pregnancy controls were genotyped. Among primiparous subjects, the frequency of “AC+CC genotype of AT1” was significantly higher in severe HP than in the controls. A multivariate analysis with “AC+CC genotype of AT1” and “TT genotype of AGT” revealed that these were independently associated with primiparous severe HP. However, when “family history of hypertension” and “prepregnancy BMI ≥25” were added as factors examined in the multivariate analysis, only “TT genotype of AGT” and “family history of hypertension” were found to be independent potent factors. The present results suggest that the C1166 allele of the AT1 gene may be concerned with the predisposition to essential hypertension independently of the T235 allele of the AGT gene.
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References
Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charru A, Clauser E, Tiret L, Cambien F, Corvol P, Soubrier F (1994) Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 24:63–69
Caulfield M, Lavender P, Farrall M, Munroe P, Lawson M, Turner P, Clark AJ (1994) Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med 330:1629–1633
Duncan JA, Scholey JW, Miller JA (2001) Angiotensin II type 1 receptor gene polymorphisms in humans: physiology and pathophysiology of the genotypes. Curr Opin Nephrol Hypertens 10:111–116
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
Hilgers KF, Langenfeld MR, Schlaich M, Veelken R, Schmieder RE (1999) 1166 A/C polymorphism of the angiotensin II type 1 receptor gene and the response to short-term infusion of angiotensin II. Circulation 100:1394–1399
Inoue I, Nakajima T, Williams CS, Quackenbush J, Puryear R, Powers M, Cheng T, Ludwig EH, Sharma AM, Hata A, Lalouel J-M (1997) A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest 99:1786–1797
Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, Corvol P (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180
Jiang Z, Zhao W, Yu F, Xu G (2001) Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension. Chin Med J (Engl) 114:1249–1251
Kobashi G, Hata A, Shido K, Kato EH, Yamada H, Fujimoto S, Kishi R, Kondo K (1999) Association of a variant of the angiotensinogen gene with pure type of hypertension in pregnancy in the Japanese: implication of a racial difference and significance of an age factor. Am J Med Genet 86:232–236
Lajemi M, Labat C, Gautier S, Lacolley P, Safar M, Asmar R, Cambien F, Benetos A (2001) Angiotensin II type 1 receptor-153A/G and 1166A/C gene polymorphisms and increase in aortic stiffness with age in hypertensive subjects. J Hypertens 19:407–413
Liyou N, Davis D, James K, Simons L, Friedlander Y, Simons J, McCallum J, Johnson A (1999) The A1166C mutation in the angiotensin II type I receptor and hypertension in the elderly. Clin Exp Pharmacol Physiol 26:525–526
Morgan T, Craven C, Lalouel JM, Ward K (1999) Angiotensinogen Thr235 variant is associated with abnormal physiologic change of the uterine spinal arteries in first-trimester decidua. Am J Obstet Gynecol 180:95–102
Nalogowska-Glosnicka K, Lacka BI, Zychma MJ, Grzeszczak W, Zukowska-Szczechowska E, Poreba R, Michalski B, Kniazewski B, Rzempoluch J, PIH Study Group (2000) Angiotensin II type 1 receptor gene A1166C polymorphism is associated with the increased risk of pregnancy-induced hypertension. Med Sci Monit 6:523–529
National High Blood Pressure Education Program Working Group (1990) Report on high blood pressure in pregnancy (Consensus Report). Am J Obstet Gynecol 163:1689–1712
Ono K, Mannami T, Baba S, Yasui N, Ogihara T, Iwai N (2003) Lack of association between angiotensin II type 1 receptor gene polymorphism and hypertension in Japanese. Hypertens Res 26:131–134
Russ AP, Maerz W, Ruzicka V, Stein U, Gross W (1993) Rapid detection of the hypertension-associated Met235→Thr allele of the human angiotensinogen gene. Hum Mol Genet 2:609–610
Schmidt S, Beige J, Walla-Friedel M, Michel MC, Sharma AM, Ritz E (1997) A polymorphism in the gene for the angiotensin II type 1 receptor is not associated with hypertension. J Hypertens 15:1385–1388
Seremak-Mrozikiewicz A, Drews K, Chmara E, Mrozikiewicz PM, Slomko Z (2000) Gestational hypertension (GH) and a1166c polymorphism of angiotensin II type 1 receptor. Ginekol Pol 71:783–788
Spiering W, Kroon AA, Fuss-Lejeune MM, Daemen MJ, de Leeuw PW (2000) Angiotensin II sensitivity is associated with the angiotensin II type 1 receptor A(1166)C polymorphism in essential hypertensives on a high sodium diet. Hypertension 36:411–416
Szombathy T, Szalai C, Katalin B, Palicz T, Romics L, Csaszar A (1998) Association of angiotensin II type 1 receptor polymorphism with resistant essential hypertension. Clin Chim Acta 269:91–100
Takami S, Katsuya T, Rakugi H, Sato N, Nakata Y, Kamitani A, Miki T, Higaki J, Ogihara T (1998) Angiotensin II type 1 receptor gene polymorphism is associated with increase of left ventricular mass but not with hypertension. Am J Hypertens 11:316–321
Tamakoshi A, Ishikawa S, Ojima T, Kikuchi S, Kobashi G, Saito Y, Sugimori H, Nakamura Y, Nakayama T, Muto K, Yamagata Z, Washio M (2000) The guideline of informed consent in epidemiological studies, ver. 1.0. Nihonijishinposya, Tokyo, pp 1–27
Ward K, Hata A, Jeunemaitre X, Helin C, Nelson L, Namikawa C, Farrington PF, Ogasawara M, Suzumori K, Tomoda S, Berrebi S, Sasaki M, Corvol P, Lifton RP, Lalouel JM (1993) A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet 4:59–61
Acknowledgements
Cordial thanks are due to the many collaborators who supplied cases and controls in the Department of Obstetrics and Gynecology of Hokkaido University Hospital and its affiliated hospitals. We would also like to express our gratitude to Dr. H. Tamashiro for advice, Ms. M. Funamizu for technical assistance and Dr. E. Nakajima for critical assistance in manuscript preparation. This work was supported in part by a grant-in-aid from the Japanese Ministry of Education, Science and Culture, a grant from the Hokkaido Foundation for the Promotion of Scientific Industrial Technology, and the 16th Research Grant of the Nakatomi Foundation.
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Kobashi, G., Hata, A., Ohta, K. et al. A1166C variant of angiotensin II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene. J Hum Genet 49, 182–186 (2004). https://doi.org/10.1007/s10038-004-0129-4
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DOI: https://doi.org/10.1007/s10038-004-0129-4
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