Endocrine Abstracts (2008) 16 P678

Association of estrogen receptor alpha and beta gene polymorphisms with sex steroid levels in men

Christina Sakka1, Zoe Efstathiadou2, Stergios Polyzos2, Maria Goutou1, Nikolaos Stakias1 & George Koukoulis1

1Endocrine Unit, Department of Internal Medicine, University of Thessaly School of Medicine, Larissa, Greece; 2Department of Endocrinology, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.

Estrogens play an important role in male physiology. We investigated the possible association of four single nucleotide polymorphisms in estrogen receptor α (ER1) and Estrogen Receptor β (ER2) genes with circulating levels of sex steroids and Sex Hormone Binding Globulin (SHBG) in men.

SHBG, total and calculated free testosterone (TT and cal FT), estradiol (E2) and free estradiol (FE2) were determined in a population based cohort of 170 apparently healthy Greek men. Body mass index (BMI), waist circumference (WC) and percentage of body fat (%fat) content were measured in all participants. Genotyping for the PvuII and XbaI polymorphisms of the ER1 gene and for the Rsa I and Alu I polymorphisms of the ER2 gene was performed.

PvuII showed an association with E2 levels (median (IQR) pp 58.5 (42.1–73.4) pmol/l versus Pp 48.8 (43–59.6) and PP 57.7 (44.8–67.1), P=0.032), and with %fat (median (IQR) pp 24.4 (20.4–27.4) pmol/l versus Pp 22.7 (19.2–25.7) and PP 22.5 (15.3–26.4), P=0.044), after adjustment for age and WC. Furthermore, the effect of PvuII on E2 was independent of %fat (P=0.038).

A synergistic effect of the 2 ER1 polymorphisms on E2 (P=0.023), FE2 (P=0.03) and %fat (P=0.004) was also present.

A synergistic effect of the ER1 and ER2 genes on TT (P=0.009), independent of age, WC and %fat also emerged.

In conclusion, genetic variation in ER1 is associated with estradiol levels and body fat content regulation in men. Furthermore, a synergistic effect of ER1 and ER2 genes is exerted on serum testosterone levels.

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