Abstract
Hypotheses about pregnancy-induced hypertension (PIH) have been proposed to explain the vascular damage that characterizes this disease. Reports indicate that estrogens and estrogen receptors play important physiological roles in cardiovascular diseases. There have been studies examining the association between coronary artery disease and the estrogen receptor α (ESR1) gene. The aim of the present work was to assess the association between PIH and single-nucleotide polymorphisms (SNPs) in the human ESR1 gene, by conducting a haplotype-based case-control study. Based on a database search at the web site of the National Center of Biotechnology Information, we chose five SNPs in the human ESR1 gene, and performed an association study using 95 PIH patients and 200 age-matched non-PIH subjects. The frequency of rs2881766 genotypes and alleles differed significantly between the two groups. There was no significant difference in overall distribution of genotypes or alleles of the other four SNPs. The T allele of rs2881766 was significantly more prevalent in the PIH group than in the non-PIH group. Haplotype-based case-control analysis revealed that there was a significant difference in overall distribution of the combinations rs2881766-rs1643821-rs988328 and rs2881766-rs1643821 between the PIH group and the non-PIH group (all or body mass index [BMI]-matched). One susceptibility haplotype for PIH and two resistance haplotypes for PIH were revealed by comparison between the PIH group and the non-PIH (BMI-matched) control group. In conclusion, the T allele of rs2881766 could be a useful genetic marker of PIH. The G-A-T haplotype of rs2881766-rs1643821-rs988328 and the G-A haplotype of rs2881766-rs1643821 appear to be resistance markers of PIH.
Similar content being viewed by others
Article PDF
References
Roberts JM, Cooper DW : Pathogenesis and genetics of pre-eclampsia. Lancet 2001; 357: 53–56.
Sohda S, Arinami T, Hamada H, Yamada N, Hamaguchi H, Kubo T : Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia. J Med Genet 1997; 34: 525–526.
Yamada N, Arinami T, Yamakawa-Kobayashi K, et al: The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia. J Hum Genet 2000; 45: 138–141.
Gurdol F, Isbilen E, Yilmaz H, Isbir T, Dirican A : The association between preeclampsia and angiotensin-converting enzyme insertion/deletion polymorphism. Clin Chim Acta 2004; 34: 127–131.
Malina AN, Laivuori HM, Agatisa PK, et al: The Trp64Arg polymorphism of the beta3-adrenergic receptor is not increased in women with preeclampsia. Am J Obstet Gynecol 2004; 190: 779–783.
Maruyama A, Nakayama T, Furuya K, Mizutani Y, Yamamoto T : Association study between the human Renin gene and preeclampsia. Hypertens Pregnancy 2005; 24: 39–48.
Sumino H, Ichikawa S, Ohyama Y, et al: Effects of hormone replacement therapy on serum angiotensin-converting enzyme activity and plasma bradykinin in postmenopausal women according to angiotensin-converting enzyme-genotype. Hypertens Res 2003; 26: 53–58.
Evans RM : The steroid and thyroid hormone receptor superfamily. Science 1988; 240: 889–895.
Walter P, Green S, Greene G, et al: Cloning of the human estrogen receptor cDNA. Proc Natl Acad Sci U S A 1985; 82: 7889–7893.
Mendelsohn ME, Karas RH : The protective effects of estrogen on the cardiovascular system. N Engl J Med 1999; 340: 1801–1811.
Mendelsohn ME : Protective effects of estrogen on the cardiovascular system. Am J Cardiol 2002; 89 ( 12 Suppl): 12E–18E.
Mishell DR Jr, Mendelsohn ME : Introduction: the role of hormone replacement therapy in prevention and treatment of cardiovascular disease in postmenopausal women. Am J Cardiol 2002; 89 ( 12 Suppl): 1E–4E.
Pare G, Krust A, Karas RH, et al: Estrogen receptor-alpha mediates the protective effects of estrogen against vascular injury. Circ Res 2002; 90: 1087–1092.
Karas RH, Schulten H, Pare G, et al: Effects of estrogen on the vascular injury response in estrogen receptor alpha, beta (double) knockout mice. Circ Res 2001; 89: 534–539.
Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM : The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001; 20 ( 1): IX–XIV.
Sato I, Nakayama T, Maruyama A, et al: Study of association between hypertensive disorders of pregnancy and the human coagulation factor XI gene. Hypertens Pregnancy 2006; 25: 21–31.
Nakayama T, Soma M, Rahmutula D, Ozawa Y, Kanmatsuse K : Isolation of the 5′-flanking region of genes by thermal asymmetric interlaced polymerase chain reaction. Med Sci Monit 2001; 7: 345–349.
Kobayashi Y, Nakayama T, Sato N, Izumi Y, Kokubun S, Soma M : Haplotype-based case-control study of adrenomedullin genes on proteinuria in the subjects with essential hypertension. Hypertens Res 2005; 28: 229–236.
Morita A, Nakayama T, Doba N, Hinohara S, Soma M : Polymorphism of the C reactive protein gene is related to serum CRP level and arterial pulse wave velocity in healthy elderly Japanese. Hypertens Res 2006; 29: 323–331.
Dempster AP, Laird NM, Rubin DB : Maximum likelihood from incomplete data via the EM algorithm. J R Stat Soc 1977; 39: 1–22.
Kaneko Y, Nakayama T, Saito K, et al: Relationship between the thromboxane A2 receptor gene and susceptibility to cerebral infarction. Hypertens Res 2006; 29: 665–671.
Burl VL, Whelton P, Roccella EJ, et al: Prevalence of hypertension in the US adult population: results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension 1995: 25: 305–313.
August P, Oparil S : Commentary: hypertension in women. J Clin Endocrinol Metab 1999; 84: 1862–1866.
Calhoun DA, Oparil S : The sexual dimorphism of high blood pressure. Cardiol Rev 1998; 6: 356–363.
Han SZ, Karaki H, Ouchi Y, Akishita M, Orimo H : 17 beta-Estradiol inhibits Ca2+ influx and Ca2+ release induced by thromboxane A2 in porcine coronary artery. Circulation 1995; 91: 2619–2626.
Morey AK, Razandi M, Pedram A, Hu RM, Prins BA, Levin ER : Oestrogen and progesterone inhibit the stimulated production of endothelin-1. Biochem J 1998; 330: 1097–1105.
Oertel GW, West CD, Eik-Nes KB : Isolation and identification of estrone, estradiol and estriol in human pregnancy plasma. J Clin Endocrinol Metab 1959; 19: 1619–1625.
Zhu Y, Bian Z, Lu P, et al: Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta. Science 2002; 295: 505–508.
Maruyama A, Nakayama T, Sato N, Mizutani Y, Furuya K, Yamamoto T : Association study using single nucleotide polymorphisms in the estrogen receptor beta (ESR2) gene for preeclampsia. Hypertens Res 2004; 27: 903–909.
Lehtimaki T, Kunnas TA, Mattila KM, et al: Coronary artery wall atherosclerosis in relation to the estrogen receptor 1 gene polymorphism: an autopsy study. J Mol Med 2002; 80: 176–180.
Shearman AM, Cupples LA, Demissie S, et al: Association between estrogen receptor alpha gene variation and cardiovascular disease. JAMA 2003; 290: 2263–2270.
Malamitsi-Puchner A, Tziotis J, Evangelopoulos D, et al: Gene analysis of the N-terminal region of the estrogen receptor alpha in preeclampsia. Steroids 2001; 66: 695–700.
Leeners B, Rath W, Kuse S, Irawan C, Imthurn B, Neumaier-Wagner P : BMI: new aspects of a classical risk factor for hypertensive disorders in pregnancy. Clin Sci (Lond) 2006; 111: 81–86.
Bodnar LM, Catov JM, Klebanoff MA, Ness RB, Roberts JM : Prepregnancy body mass index and the occurrence of severe hypertensive disorders of pregnancy. Epidemiology 2007; 18: 234–239.
Morris RW, Kaplan NL : On the advantage of haplotype analysis in the presence of multiple disease susceptibility alleles. Genet Epidemiol 2002; 23: 221–233.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tamura, M., Nakayama, T., Sato, I. et al. Haplotype-Based Case-Control Study of Estrogen Receptor α (ESR1) Gene and Pregnancy-Induced Hypertension. Hypertens Res 31, 221–228 (2008). https://doi.org/10.1291/hypres.31.221
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.31.221
Keywords
This article is cited by
-
Genetic variations in estrogen and progesterone pathway genes in preeclampsia patients and controls in Bavaria
Archives of Gynecology and Obstetrics (2021)
-
A case–control study between the STIM1 gene and hypertensive disorders of pregnancy
Hypertension Research (2018)
-
Estrogen synthesis genes CYP19A1, HSD3B1, and HSD3B2 in hypertensive disorders of pregnancy
Endocrine (2012)
-
Association between ESR1 and ESR2 gene polymorphisms and hyperlipidemia in Chinese Han postmenopausal women
Journal of Human Genetics (2010)