INFLUENCE OF A MULTIGENIC MODEL ON BMD AND SERUM ESTRADIOL IN YOUNG WOMEN

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Both the 17β-hydroxysteriod dehydrogenase 1 (17β-HSD1) and cytochrome P450c17α (CYP17) genes are involved in estrogen metabolism. Recently, a multigenic model utilizing these two genes was demonstrated to be related to breast cancer risk, with the hypothesis that this effect was due to altered levels of circulating estrogens. PURPOSE: This investigation was performed to test the hypothesis that this multigenic model would also predict bone mineral density (BMD) in college-aged young women, with the A/A genotype of 17β-HSD1 and the A2/A2 genotype of CYP17 suggested to te associated with elevated levels of both BMD and E2. METHODS: Forty-five young women aged 21 ± 3 years (X±SD) participated in this investigation. 17β-HSD1 and CYP17 genotypes were determined via PCR as A/A, A/G, or G/G, and A1/A1, A1/A2, or A2/A2, respectively. Subjects were assigned to three groups by the number of A and A2 alleles present (0–1, 2, and 3–4 alleles). BMD was assessed at the proximal femur (Ward's triangle (W)) by dual energy x-ray absorptiometry (DXA). Serum E2 (fasting, day 22) was assessed by RIA. Weekly physical activity patterns were derived from questionnaires. BMD and E2 differences between wome of the differing genotype groups were determined by multivariate analysis of variance (with ethnicity, weight, gynecologic age and normalized minutes of physical activity as the covariates for BMD). RESULTS: Results are presented as X ± SD. *Significantly different from Group 2, +significantly different from Group 1 (p < 0.05).TableWhile luteal phase E2 concentrations were higher in those with more of the A and A2 alleles, the pattern was less clear for WBMD. CONCLUSION: These results suggest that other genes should be added to this multigenic model to enhance its prediction of BMD. Supported by USC James H. Zumberge Faculty Research and Innovation Fund, USC MFWA Research Fund, and BCRP 1KB-0060