Apolipoprotein E gene determines serum testosterone and dehydroepiandrosterone levels in postmenopausal women

Objective: Apolipoprotein E (ApoE) is believed to play an important role in lipid metabolism and has been found to be related to diseases associated with ageing, the important characteristic of which is decline in circulating sex steroids, including androgen. Design: To find the relationships of levels of serum testosterone and its precursor, dehydroepiandrosterone (DHEA), to ApoE polymorphism in 113 postmenopausal Caucasian women. Methods: The ApoE genotype was assessed by polymerase chain reaction and CfoI endonuclease digestion. ApoE genotype distribution was as follows: E2/3, 15%; E3/3, 71.7%; E2/4, 1.8%; E3/4, 10.6; and E4/4, 0.89%. The differences in serum androgen levels between genotypes were evaluated by ANCOVA and least significant difference (LSD) multiple comparisons test after adjustment for body mass index, age and/or years since menopause. Results: Significant intergroup differences between the most frequent allele combination (2/3, 3/3 and 3/4) in serum DHEA levels were found (P < 0.05, ANCOVA). DHEA levels were higher in women with the E3/4 allele combination than in the E3/3 genotype (P < 0.01, LSD multiple comparisons). In serum testosterone levels, borderline intergroup differences were found (P < 0.07, ANCOVA). Higher testosterone levels were found in the E3/4 allele combination as compared with E3/3 (P < 0.05, LSD multiple comparisons). Dose effect of E4 allele analysis indicated higher serum DHEA and testosterone levels in women with the E4 allele present than in women with the E4 allele absent (P < 0.003 for DHEA, P < 0.007 for testosterone, ANCOVA). Conclusions: Circulating testosterone and DHEA are associated with the ApoE genotype, which may render women missing the allele E4 more susceptible to the development of some diseases associated with ageing and menopause.