Abstract
Objective: Deficiency of the gene encoding endothelial nitric oxide synthase, i.e. Nos3, has been reported to be associated with late menarche, reduced ovulation rates,
fewer deliveries, and earlier onset of menopause in a mouse model. Methods: We assessed the Glu298Asp and the T-786C polymorphisms of Nos3 in 87 consecutive healthy postmenopausal women by pyro- and capillary-sequencing,
respectively. Results were correlated with age at menarche and natural menopause,
number of miscarriages and live births, as well as body mass index (BMI) and smoking
habits. Results: Allelic frequencies of the Glu298Asp polymorphism of Nos3 were 121 (69.5%) and 53 (30.5%) for the wild-type G allele and the mutant T allele,
respectively. Forty-one women (47.1%) were homozygote wild-type (G/G), 39 (44.9%)
were heterozygote (G/T), and 7 (8.0%) were homozygote mutant (T/T). Allelic frequencies
of the T-786C polymorphism of Nos3 were 105 (60.6%) and 69 (39.4%) for the wild-type T allele and the mutant C allele,
respectively. Thirty-three women (38.0%) were homozygote wild-type (T/T), 39 (45.1%)
were heterozygote (T/C), and 15 (16.9%) were homozygote mutant (C/C). Presence of
at least one mutant allele of the Glu298Asp or the T-786C polymorphisms of Nos3 were not associated with age at menarche, natural menopause, and number of miscarriages
and deliveries. BMI above 27 kg/m2 and smoking were associated with earlier onset of natural menopause (47.8 years versus
50.2 years (P=0.01) and 46.8 years versus 49.8 years (P=0.02)). Conclusions: Our data show that smoking and increased BMI, but not Glu298Asp or the T-786C polymorphisms
of Nos3, are associated with an early onset of natural menopause.
Keywords
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References
- The variability of female reproductive ageing.Hum. Reprod. Update. 2002; 8: 141-154
- Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors.Fertil. Steril. 1997; 68: 95-102
- The role of genetic factors in age at natural menopause.Hum. Reprod. 2001; 16: 2014-2018
- Factors associated with early menopause.Maturitas. 2000; 35: 3-9
- Family history as a predictor of early menopause.Fertil. Steril. 1995; 64: 740-745
- Estrogen receptor polymorphism predicts the onset of natural and surgical menopause.J. Clin. Endocrinol. Metab. 1999; 84: 3146-3150
- Mothers and daughters menopausal ages: is there a link.Eur. J. Obstet. Gynecol. Reprod. Biol. 1997; 74: 63-66
- Genetic influences on the age at menopause.Lancet. 1998; 352: 1084-1085
- Endothelial nitric oxide synthase gene polymorphism in women with idiopathic recurrent miscarriage.Hum. Reprod. 2001; 16: 1644-1647
- Perinatal development of endothelial nitric oxide synthase-deficient mice.Biol. Reprod. 2001; 64: 666-673
- Genetic contributions of the endothelial nitric oxide synthase gene to ovulation and menopause in a mouse model.Fertil. Steril. 2000; 73: 1025-1031
- Nitric oxide: physiology, pathophysiology, and pharmacology.Pharmacol. Rev. 1991; 43: 109-142
- Endothelial nitric oxide synthase gene is positively associated with essential hypertension.Hypertension. 1998; 32: 3-8
- A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis.Stroke. 2001; 32: 735-740
- Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer.Gynecol. Oncol. 2002; 86: 134-137
- Polymorphisms of the angiotensinogen gene, the endothelial nitric oxide synthase gene, and the interleukin-1beta gene promoter in women with idiopathic recurrent miscarriage.Mol. Hum. Reprod. 2002; 8: 95-100
- The missense Glu298Asp variant of the endothelial nitric oxide synthase gene is strongly associated with placental abruption.Hum. Genet. 2001; 108: 181-183
- Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with severe preeclampsia.J. Soc. Gynecol. Investig. 2000; 7: 238-241
- T-786→C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm.Circulation. 1999; 99: 2864-2870
- The T-786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients.J. Am. Coll. Cardiol. 2003; 41: 938-945
- T-786C polymorphism in endothelial NO synthase gene affects cerebral circulation in smokers: possible gene–environmental interaction.Arterioscler. Thromb. Vasc. Biol. 2002; 22: 605-610
- Smoking, body mass index, socioeconomic status and the menopausal transition in a British national cohort.Int. J. Epidemiol. 2000; 29: 845-851
- Risks of smoking to reproductive health. Assessment of women’s knowledge.Am. J. Obstet. Gynecol. 2001; 184: 934-939
- Prospective study of factors influencing the onset of natural menopause.J. Clin. Epidemiol. 1998; 51: 1290-1292
- Prospective study of the determinants of age at menopause.Am. J. Epidemiol. 1997; 145: 124-133
- A polymorphism of the Nos3 gene and age at natural menopause.Fertil. Steril. 2002; 78: 1184-1186
Article info
Publication history
Accepted:
January 7,
2004
Received in revised form:
December 9,
2003
Received:
April 15,
2003
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
