Objective: The aim of this study is the characterizing of genetic variation in PvuII and XbaI polymorphisms of the ESR1 gene associated with age-dependent endocrine, metabolic and cognitive changes in a representative sample of Romanian population stratified by age and sex.
Subjects and methods: Subjects, both genders aged between 20 and 80 yr were assigned to three lots 1) 177 subjects aged 5580 years with moderately cognitive impairment (MCI) (MMSE<28); 2) 133 age-matched subjects without cognitive impairment (MMSE≥28); 3) 143 healthy subjects under 55 years. The haematological, biochemical profiles and cognitive performance were evaluated. Gene polymorphisms were assayed by using PCR-RFLP technique.
Results: The hematological, biochemical and hormonal profiles, correlated with the cognition and associated with both PvuII (IVS1-397 T/C) and XbaI (IVS1-351 A/G) polymorphisms proved that the aging process produces profound changes.
The frequencies of genotypes and alleles of polymorphisms did not deviate from the Hardy-Weinberg equilibrium in lot 3 (under 55yr) and lot 1 with MCI. Of note, in men compared with women as whole group and in lot 2 (over 55 yr) neither the PvuII nor the XbaI genotypes were in Hardy-Weinberg equilibrium (P<0.004)). In older peoples (lot 2) there were significant differences between distributions of PvuII and XbaI genotypes compared to younger peoples. The percentages of both CC and AA genotypes significantly decreased whereas TC and AG genotypes increased with advanced age. The changes in endocrine function that involved a decrease of testosterone, DHEA, estrogens, TSH, growth hormone, insulin-like growth factor-1 concomitant with an increase of LH and FSH were associated with both PvuII and XbaI polymorphisms.
Concusions: Our results showed that the C and G alleles in ESR1 polymorphisms are associated with the endocrine, metabolic and cognitive alterations with advanced age. Further research is needed to determine the mechanism whereby ESR1 polymorphisms influence aging.
This work was supported by grant PN II no. 41-014/2007.
25 - 29 Apr 2009
European Society of Endocrinology