Apolipoprotein E gene determines serum testosterone and dehydroepiandrosterone levels in postmenopausal women. 2002

Ivana Zofková, and Katerina Zajícková, and Martin Hill, and Ales Horínek
Institute of Endocrinology, Narodni 8, Prague 1 116 94, Czech Republic. izofko@endo.cz

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. METHODS 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 carrying the allele E4 more susceptible to the development of some diseases associated with ageing and menopause [corrected].

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D003430 Cross-Sectional Studies Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time. Disease Frequency Surveys,Prevalence Studies,Analysis, Cross-Sectional,Cross Sectional Analysis,Cross-Sectional Survey,Surveys, Disease Frequency,Analyses, Cross Sectional,Analyses, Cross-Sectional,Analysis, Cross Sectional,Cross Sectional Analyses,Cross Sectional Studies,Cross Sectional Survey,Cross-Sectional Analyses,Cross-Sectional Analysis,Cross-Sectional Study,Cross-Sectional Surveys,Disease Frequency Survey,Prevalence Study,Studies, Cross-Sectional,Studies, Prevalence,Study, Cross-Sectional,Study, Prevalence,Survey, Cross-Sectional,Survey, Disease Frequency,Surveys, Cross-Sectional
D003687 Dehydroepiandrosterone A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion. Dehydroisoandrosterone,Prasterone,5-Androsten-3-beta-hydroxy-17-one,5-Androsten-3-ol-17-one,Androstenolone,DHEA,Prasterone, 3 alpha-Isomer,5 Androsten 3 beta hydroxy 17 one,5 Androsten 3 ol 17 one,Prasterone, 3 alpha Isomer
D005260 Female Females
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D001057 Apolipoproteins E A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III. Apo-E,Apo E,Apo E Isoproteins,ApoE,Apolipoprotein E Isoproteins,Apoprotein (E),Apoproteins E,Isoproteins, Apo E,Isoproteins, Apolipoprotein E
D013739 Testosterone A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL. 17-beta-Hydroxy-4-Androsten-3-one,17-beta-Hydroxy-8 alpha-4-Androsten-3-one,8-Isotestosterone,AndroGel,Androderm,Andropatch,Androtop,Histerone,Sterotate,Sustanon,Testim,Testoderm,Testolin,Testopel,Testosterone Sulfate,17 beta Hydroxy 4 Androsten 3 one,17 beta Hydroxy 8 alpha 4 Androsten 3 one,8 Isotestosterone

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