title: A microsatellite polymorphism in IGF1 gene promoter and timing of natural menopause in Caucasian women.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1. Department of Human Biological Development, Institute of Anthropology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Kaczmarek
authors.affiliation: 2. Department of Animal Physiology, Institute of Experimental Biology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Pacholska-Bogalska
authors.affiliation: 3. Department of Gynaecological Oncology and Gynaecology, Medical University, Lublin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kwaśniewski
authors.affiliation: 3. Department of Gynaecological Oncology and Gynaecology, Medical University, Lublin, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Kotarski
authors.affiliation: 4. Department of Obstetrics, Endocrinology and Gynaecology, Poznań University of Medical Sciences, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Halerz-Nowakowska
authors.affiliation: 5. Department of Molecular Virology, Institute of Experimental Biology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Goździka-Józefiak
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008572:Menarche / Q000235:genetics; D008593:Menopause / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D044465:White People / Q000235:genetics
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I
keywords: IGF1 gene; age at menarche; age at natural menopause; candidate gene approach; cytosine-adenine (CA) microsatellite polymorphism; smoking status