Association between a Variant of the Glutathione S-Transferase P1 Gene (GSTP1) and Hypertension in Pregnancy in Japanese: Interaction with Parity, Age, and Genetic Factors

ABSTRACT

Hypertension in pregnancy (HP), including preeclampsia (PE), is known to be a multifactorial disease. Recently, an Ile105Val variant of the glutathione S-transferase P1 gene (GSTP1) was shown to be associated with PE in The Netherlands. We therefore performed an association study of the Ile105Val variant comparing 131 patients with HP and 327 normal pregnant controls in Japan. We analyzed the data in the context of other risk factors before pregnancy. The frequency of the Ile/Val+Val/Val genotype of the GSTP1 was not significantly different between the HP (26%) patients and the controls (28%). However, in primiparous patients, the frequency was significantly different in elderly pregnancy (63% in severe HP vs. 18% in controls; P < 0.05), in the subgroup with the MM+MT genotypes of the angiotensinogen gene (50% in severe HP vs. 26% in controls; P < 0.05), and in the subgroup with the GA+AA genotypes of the endothelial nitric oxide synthase gene (42% in severe HP vs. 13% in controls; P < 0.05). These results suggest that this variant of the GSTP1 may play a role in the manifestation of HP together with other independently and/or synergistically acting factors, particularly in primiparous pregnancy.

KEYWORDS

Glutathione S-transferase P1 - preeclampsia - angiotensinogen - nitric oxide synthase - synergism

REFERENCES

• 1 Broughton Pipkin F, Rubin P C. Pre-eclampsia-the `disease of theories.'  Br Med Bull . 1994;  50 381-396
• 2 Ward K, Hata A, Jeunemaitre X. et al . A molecular variant of angiotensinogen associated with preeclampsia.  Nat Genet . 1993;  4 59-61
• 3 Kobashi G. A case-control study of pregnancy-induced hypertension with a genetic predisposition: association of a molecular variant of angiotensinogen in the Japanese women.  Hokkaido Igaku Zasshi . 1995;  70 649-657
• 4 Yoshimura T, Yoshimura M, Tabata A. et al . Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with severe preeclampsia.  J Soc Gynecol Invest . 2000;  7 238-241
• 5 Kobashi G, Yamada H, Ohta K, Kato E, Ebina Y, Fujimoto S. Endothelial nitric oxide synthase gene (NOS3) variant and hypertension in pregnancy.  Am J Med Genet . 2001;  103 241-244
• 6 Kobashi G, Yamada H, Asano T. et al . The factor V Leiden mutation is not a common cause of pregnancy-induced hypertension in Japan.  Semin Thromb Hemost . 1999;  25 487-489
• 7 Sohda S, Arinami T, Hamada H. et al . Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia.  J Med Genet . 1997;  34 525-526
• 8 Kobashi G, Yamada H, Asano T. et al . Absence of association between a common mutation in the methylenetetrahydrofolate reductase gene and preeclampsia in Japanese women.  Am J Med Genet . 2000;  93 122-125
• 9 Li J, Brasier A R. Angiotensinogen gene activation by angiotensin II is mediated by the rel A (nuclear factor-kappa B p65) transcription factor: one mechanism for the renin angiotensin system positive feedback loop in hepatocytes.  Mol Endocrinol . 1996;  10 252-264
• 10 Kobashi G, Hata A, Shido K. et al . 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 . 1999;  86 232-236
• 11 Inoue I, Nakajima T, Williams C S. et al . A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.  J Clin Invest . 1997;  99 1786-1797
• 12 Schmidt H H, Walter U. NO at work.  Cell . 1994;  78 919-925
• 13 Lefer A M. Nitric oxide: nature's naturally occurring leukocyte inhibitor.  Circulation . 1997;  95 553-554
• 14 Seligman S P, Buyon J P, Clancy R M, Young B K, Abramson S B. The role of nitric oxide in the pathogenesis of preeclampsia.  Am J Obstet Gynecol . 1994;  171 944-948
• 15 Lyall F, Young A, Greer I A. Nitric oxide concentrations are increased in the feto-placental circulation in preeclampsia.  Am J Obstet Gynecol . 1995;  173 714-718
• 16 Nasiell J, Nisell H, Blanck A, Lunell N O, Faxen M. Placental expression of endothelial constitutive nitric oxide synthase mRNA in pregnancy complicated by preeclampsia.  Acta Obstet Gynecol Scand . 1998;  77 492-496
• 17 Norris L A, Higgins J R, Darling M R, Walshe J J, Bonnar J. Nitric oxide in the uteroplacental, fetoplacental, and peripheral circulations in preeclampsia.  Obstet Gynecol . 1999;  93 958-963
• 18 Yoshimura M, Yasue H, Nakayama M. et al . A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese.  Hum Genet . 1998;  103 65-69
• 19 Shimasaki Y, Yasue H, Yoshimura M. et al . Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction.  J Am Coll Cardiol . 1998;  31 1506-1510
• 20 Hingorani A D, Liang C F, Fatibene J. et al . A common variant of the endothelial nitric oxide synthase (Glu298→Asp) is a major risk factor for coronary artery disease in the UK.  Circulation . 1999;  100 1515-1520
• 21 Zusterzeel P L, Visser W, Peters W H. et al . Polymorphism in the glutathione S-transferase P1 gene and risk for preeclampsia.  Obstet Gynecol . 2000;  96 50-54
• 22 Watson M A, Stewart R K, Smith G B, Massey T E, Bell D A. Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution.  Carcinogenesis . 1998;  19 275-280
• 23 National High Blood Pressure Education Program Working Group. Report on High Blood Pressure in Pregnancy.  Am J Obstet Gynecol . 1990;  163 1691-1712
• 24 Tamakoshi A, Ishikawa S, Ojima T. et al .The Guidelines for Informed Consent in Epidemiological Studies, Version 1.0 Tokyo: Nihonijishinposya; 2000: 1-27
• 25 Harries L W, Stubbins M J, Forman D, Howard G C, Wolf C R. Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer.  Carcinogenesis . 1997;  18 641-644
• 26 Russ A P, Maerz W, Ruzicka V, Stein U, Gross W. Rapid detection of the hypertension-associated Met235→Thr allele of the human angiotensinogen gene.  Hum Mol Genet . 1993;  2 609-610
• 27 Gonzalez F J, Gelboin H V. Role of human cytochrome P-450s in risk assessment and susceptibility to environmentally based disease.  J Toxicol Environ Health . 1993;  40 289-308
• 28 Beckett G J, Hayes J D. Glutathione S-transferases: biomedical applications.  Adv Clin Chem . 1993;  30 281-380
• 29 Hayes J D, Pulford D J. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.  Crit Rev Biochem Mol Biol . 1995;  30 445-600
• 30 van Lieshout M E, Roelofs H M, Dekker S. et al . Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma.  Cancer Res . 1999;  59 586-589
• 31 Pacifici G M, Franchi M, Colizzi C, Giuliani L, Rane A. Glutathione S-transferase in humans: development and tissue distribution.  Arch Toxicol . 1988;  61 265-269
• 32 Yamamura K, Kiyohara C, Nakanishi Y, Takayama K, Hara N. Lung cancer risk and genetic polymorphism at the glutathione S-transferase P1 locus in male Japanese.  Fukuoka Igaku Zasshi . 2000;  91 203-206
• 33 Kihara M, Kihara M, Noda K. Lung cancer risk of the GSTM1 null genotype is enhanced in the presence of the GSTP1 mutated genotype in male Japanese smokers.  Cancer Lett . 1999;  137 53-60
• 34 Katoh T, Kaneko S, Takasawa S. et al . Human glutathione S-transferase P1 polymorphism and susceptibility to smoking related epithelial cancer; oral, lung, gastric, colorectal and urothelial cancer.  Pharmacogenetics . 1999;  9 165-169
• 35 Morita S, Yano M, Tsujinaka T. et al . Association between genetic polymorphisms of glutathione S-transferase P1 and N-acetyltransferase 2 and susceptibility to squamous-cell carcinoma of the esophagus.  Int J Cancer . 1998;  79 517-520
• 36 Chesley L C, Lindheimer. Renal hemodynamics and intravascular volume in normal and hypertensive pregnancy. In: Rubin PC, ed. Handbook of Hypertension, Vol 10: Hypertension in Pregnancy. Amsterdam: Elsevier 1988: 38-65
• 37 Musey V C, Collins D C, Brogan D R. et al . Long term effects of a first pregnancy on the hormonal environment: estrogens and androgens.  J Clin Endocrinol Metab . 1987;  64 111-118
• 38 Wang D Y, de Stavola L B, Bulbrook R D. et al . The permanent effect of reproductive events on blood prolactin levels and its relation to breast cancer risk: a population study of postmenopausal women.  Eur J Cancer Clin Oncol . 1988;  24 1225-1231
• 39 Dybing E, Soderlund E J. Situations with enhanced chemical risks due to toxicokinetic and toxicodynamic factors.  Regul Toxicol Pharmacol . 1999;  30 S27-S30
• 40 Morgan T, Craven C, Lalouel J M, Ward K. Angiotensinogen Thr235 variant is associated with abnormal physiologic change of the uterine spiral arteries in first-trimester decidua.  Am J Obstet Gynecol . 1999;  180 95-102
• 41 Philip I, Plantefeve G, Vuillaumier-Barrot S. et al . G894T polymorphism in the endothelial nitric oxide synthase gene is associated with an enhanced vascular responsiveness to phenylephrine.  Circulation . 1999;  99 3096-3098
• 42 McGuire J J, Anderson D J, McDonald B J, Narayanasami R, Bennett B M. Inhibition of NADPH-cytochrome P450 reductase and glyceryl trinitrate biotransformation by diphenyleneiodonium sulfate.  Biochem Pharmacol . 1998;  56 881-893
• 43 Kurz M A, Boyer T D, Whalen R, Peterson T E, Harrison D G. Nitroglycerin metabolism in vascular tissue: role of glutathione S-transferases and relationship between NO and NO2- formation.  Biochem J . 1993;  292 545-550