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

Abstract

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.

ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations

“…ApoE expression may influence HPA axis function, as it has been implicated as a modulator of steroidogenesis in the adrenal gland (Reyland et al, 1991;Thorngate et al, 2002;Zofková et al, 2002). In plasma, E2/E2 mice had markedly elevated apoE concentrations.…”

Obesity occurring in apolipoprotein E-knockout mice has mild effects on fertility

“…Why was there no change in ovarian TC and TG concentrations, despite the presence of more lipid in the ovaries of Apoe K/K mice? In fact, although APOE is the most important supplier of the cholesterol precursor for steroid hormone production in steroidogenic tissues, it is unrelated to extracellular lipid transport (Mahley & Rall 2000, Zofkova et al 2002. The lipid droplets appear to be complex, metabolically active organelles that are directly involved in membrane traffic and possibly phospholipid recycling.…”

Effect of APOE polymorphism on obesity and lipid profile in women of differing reproductive status

“…Quite surprisingly, the mean value of the central obesity indicator (WHR) was lower in the APOE*4 carriers. Based on results of a cross-sectional study of 113 Caucasian postmenopausal women aged 62.4±9.8 years published by Zofkova et al [29], women possessing the APOE*4 allele had significantly higher serum testosterone and dehydroepiandrosterone (DHEA) levels than those lacking the APOE*4 allele. Studies have reported that dehydroepiandrosterone-S (DHEA-S, DHEA metabolite) levels are higher in lean women than in obese ones [30,31].…”