objective:We wished to determine whether genetic variability in the gene encoding endothelial nitric oxide synthase (eNOS) modifies individual susceptibility to the development of preeclampsia.
Methods:The study involved 132 preeclamptic and 113 healthy control pregnant women who were genotyped for the Glu298Asp polymorphism in the eNOS gene. X2 analysis was used to assess genotype and allele frequency differences between preeclamptic women and controls.
Results:A statistically similar allelic distribution of eNOS Glu298Asp polymorphism was observed in the two groups, with the frequency of the variant G allele being 74.6% in the preeclampsia group and 67.7% in the control group (P = .91; odds rato 1.40, 95% confidence interval 0.95, 2.01). Accordingly, the genotype distribution of the NOS polymorphism in the preeclamptic and control groups was found to be similar (P = .233).
Conclusion:These genotype data in subjects from eastem Finland were not suggestive of an important contribution of the Glu298Asp polymorphism in the NOS gene on preeclampsia across populations. However, the observed association between the Gallele and disease risk, of borderline significance, may imply that other polymorphism(s) in the gene may modify disease risk.
1. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature1980;288:373-376.
2.
2. Rapoport RM, Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res1983;52:352-357.
3.
3. Hogg N, Kalyanaraman B, Joseph J, Struck A, Parthasarathy S. Inhibition of low-density lipoprotein oxidation by nitric oxide. Potential role in atherogenesis. FEBS Lett1993;334:170-174.
4.
4. Robinson LJ, Weremowicz S, Morton CC, Michel T. Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene. Genomics1994;19:350-357.
5.
5. Hingorani AD, Liang CF, 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. Circulation1999;100:1515-1520.
6.
6. Miyamoto Y, Saito Y, Kajiyama N, et al. Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension1998;32:3-8.
7.
7. Tesauro M, Thompson WC, Rogliani P, Qi L, Chaudhary PP, Moss J. Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: Cleavage of proteins with aspartate vs glutamate at position 298. Proc Natl Acad Sci U S A2000;97:2832-2835.
8.
8. Sladek SM, Magness RR, Conrad KP. Nitric oxide and pregnancy. Am J Physiol1997;272:R441-R463.
9.
9. Yallampalli C, Garfield RE. Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of preeclampsia. Am J Obstet Gynecol1993;169:1316-1320.
10.
10. Nobunaga T, Tokugawa Y, Hashimoto K, et al. Plasma nitric oxide levels in pregnant patients with preeclampsia and essential hypertension. Gynecol Obstet Invest1996;41:189-193.
11.
11. Smarason AK, Allman KG, Young D, Redman CW. Elevated levels of serum nitrate, a stable end product of nitric oxide, in women with pre-eclampsia. Br J Obstet Gynaecol1997;104:538-543.
12.
12. Seligman SP, Buyon JP, Clancy RM, Young BK, Abramson SB. The role of nitric oxide in the pathogenesis of preeclampsia. Am J Obstet Gynecol1994;171:944-948.
13.
13. Lopez-Jaramillo P, Narvaez M, Calle A, et al. Cyclic guanosine 3′,5′ monophosphate concentrations in pre-eclampsia: Effects of hydralazine. Br J Obstet Gynaecol1996;103:33-38.
14.
14. Napolitano M, Miceli F, Calce A, et al. Expression and relationship between endothelin-1 messenger ribonucleic acid (mRNA) and inducible/endothelial nitric oxide synthase mRNA isoforms from normal and preeclamptic placentas. J Clin Endocrinol Metab2000;85:2318-2323.
16. Bashford MT, Hefler LA, Vertrees TW, Roa BB, Gregg AR. Angiotensinogen and endothelial nitric oxide synthase gene polymorphisms among Hispanic patients with preeclampsia. Am J Obstet Gynecol2001;184:1345-1350.
17.
17. Yoshimura T, Yoshimura M, Tabata A, Yasue H, Okamura H. The missense Glu298Asp variant of the endothelial nitric oxide synthase gene is strongly associated with placental abruption. Hum Genet2001;108:181-183.
18.
18. 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 Investig2000;7:238-241.
19.
19. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol2000;183:S1-S22.
20.
20. Chen G, Wilson R, Wang SH, Zheng HZ, Walker JJ, McKillop JH. Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in preeclampsia. Clin Exp Immunol1996;104:154-159.
21.
21. Ward K, Hata A, Jeunemaitre X, et al. A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet1993;4:59-61.
22.
22. Chen G, Wilson R, Boyd P, et al. Normal superoxide dismutase (SOD) gene in pregnancy-induced hypertension: Is the decreased SOD activity a secondary phenomenon?Free Radic Res1994;21:59-66.
23.
23. Dizon-Townson DS, Nelson LM, Easton K, Ward K. The factor V Leiden mutation may predispose women to severe preeclampsia. Am J Obstet Gynecol1996;175:902-905.
24.
24. Sohda S, Arinami T, Hamada H, Yamada N, Hamaguchi H, Kubo T. Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia. J Med Genet1997;34:525-526.
25.
25. Peltonen L, Jalanko A, Varilo T. Molecular genetics of the Finnish disease heritage. Hum Mol Genet1999;8:1913-1923.
