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23 October 2017

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Int J Med Sci 2015; 12(1):32-41. doi:10.7150/ijms.9840

Research Paper

A Microsatellite Polymorphism in IGF1 Gene Promoter and Timing of Natural Menopause in Caucasian Women

Maria Kaczmarek1✉, Joanna Pacholska-Bogalska2, Wojciech Kwaśniewski3, Jan Kotarski3, Barbara Halerz-Nowakowska4, Anna Goździka-Józefiak5

1. Department of Human Biological Development, Institute of Anthropology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poland
2. Department of Animal Physiology, Institute of Experimental Biology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poland
3. Department of Gynaecological Oncology and Gynaecology, Medical University, Lublin, Poland
4. Department of Obstetrics, Endocrinology and Gynaecology, Poznań University of Medical Sciences, Poland
5. Department of Molecular Virology, Institute of Experimental Biology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poland

Abstract

Background: Genes involved in the IGF-1 aging pathways in the human ovary can be considered strong candidates for predictors of the natural menopause timing. This study evaluates the association between a cytosine-adenine (CA) microsatellite polymorphism in the IGF1 gene promoter P1 and age at natural menopause.

Methods: Genomic DNA was extracted from the peripheral blood, PCR was performed using primers designed to amplify the polymorphic (CA)n repeat of the human IGF1 gene, an allele dose effect for the most common (CA)19 repeats allele, Cox proportional hazard regression models and the Kaplan-Meier cumulative survivorship method with the log-rank test were used to determine statistical significance of studied associations in a sample of 257 Polish women aged 40-58 years.

Results: Crude Cox proportional hazard regression analysis confirmed the association between the IGF1 gene polymorphism and the menopause timing (p=0.038). This relationship remained statistically significant after controlling for other menopause confounders in multivariate modelling. Out of the input variables, the (CA)n polymorphism in the IGF1 gene promoter, age at menarche and smoking status were independent covariates of the natural menopause timing (χ2 =12.845; df=3; p=0.034). The onset of menopause at a younger age was likely associated with the IGF1 genotype variant not carrying the (CA)19 repeats allele, menarche before the age of 12 and a current cigarette smoker status (HR=1.6).

Conclusion: This study provides evidence that a common cytosine-adenine (CA) microsatellite repeat polymorphism in the P1 promoter region of the IGF1 gene is an independent predictive factor for age at natural menopause in Caucasian women also after adjusting for other menopause covariates.

Keywords: candidate gene approach, cytosine-adenine (CA) microsatellite polymorphism, IGF1 gene, age at natural menopause, age at menarche, smoking status

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Kaczmarek M, Pacholska-Bogalska J, Kwaśniewski W, Kotarski J, Halerz-Nowakowska B, Goździka-Józefiak A. A Microsatellite Polymorphism in IGF1 Gene Promoter and Timing of Natural Menopause in Caucasian Women. Int J Med Sci 2015; 12(1):32-41. doi:10.7150/ijms.9840. Available from http://www.medsci.org/v12p0032.htm