Objective: The aim of this study was the identification of eNOS (G894T), p22phox (−930 A/G) and apoE gene polymorphisms associated with the impact of age-dependent endocrine changes.
Subjects and methods: Subjects, both genders, were recruited and classified into the three groups: (1) 100 subjects aged 5580+ years with mild cognitive impairment (MCI) (MMSE<28); (2) 165 age-matched subjects without cognitive impairment (MMSE>28); (3) 93 healthy subjects under 55 years. Serum cortisol, 17-OHP, DHEA, DHEAS, androstendion, estradiol, estrone, testosterone, free testosterone, DHT, SHBG, inhibin A and inhibin B, LH, FSH, Prl, GH, IGF1 were measured. Gene polymorphisms were assayed by using RFLP technique.
Results: The frequency of genotypes and alleles of eNOS and p22phox in studied groups were not significantly different. Distribution of ε2 allele of apoE gene was higher in MCI (28.3%) as compared with healthy ones (14.6%) or adults (9.6%). Rare allele apoE ε4 presented a higher frequency in MCI (17%) as compared with healthy ones (12.5%). Raised plasma cholesterol and triglycerides were found in ε2 and ε4 carriers in MCI. In the group of adult subjects the eNOS polymorphism was significantly associated with cortisol (τ2=10.36; P=0.006), DHEA (τ2=7.62; P=0.02) and DHEAS (τ2=6.94; P=0.03. In the elderly, the eNOS variant correlated significantly with BMI (τ2=6.47; P=0.04) and FSH (τ2=6.93; P=0.03); p22phox was associated at the border of significance with DHEAS (τ2=5.68; P=0.058) and ADION (τ2=5.84; P=0.054). Multivariate regression analysis for eNOS G894T in the presence of associated variables showed that DHEA (OR=0.82; 95%CI=0.690.98; P=0.032) and FAI (OR=0.95; 95%CI=0.91.0; P=0.034) were associated with age.
Conclusions: The frequency of ε2 and ε4 variants of apoE gene raised in the elderly, particularly in those with MCI. The correlation between DHEA with age seemed to be influence by the presence of both T allele of eNOS G894T and G allele of p22phox.
03 - 07 May 2008
European Society of Endocrinology