An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men

Abstract

Objective: To describe the influence of the TTTA aromatase polymorphism (TTTAn) on the relation between obesity and plasma estradiol (E(2)) in obese men.

Design: A 2-year cohort study.

Setting: Clinical research center.

Patient(s): Severely obese men (31 who had had gastric bypass surgery and 118 controls).

Intervention(s): Men were genotyped for the TTTAn CYP19A1 polymorphism. Anthropomorphic measures, plasma E(2), and other hormonal levels were determined at baseline and 2-year follow-up.

Main outcomes measure(s): Relationships between weight and changes in weight and plasma E(2) were examined in relation to the TTTAn polymorphism.

Result(s): The mean age was 46.5 ± 10.82 years, and mean body mass index was 47.1 ± 8.46 kg/m(2). The most common repeats were 7 and 11. TTTAn number did not correlate with plasma E(2) in the univariate analysis. When patients were stratified per weight group, the correlation between plasma E(2) and weight was seen only among men with a higher TTTA repeat at baseline and 2 years. Similarly, only men with higher TTTA exhibited reduced E(2) levels after weight loss.

Conclusion(s): A higher TTTA repeat is associated with a strengthened relationship between obesity and E(2). The well-established effect of increased weight on plasma E(2) appears to be absent in men with low TTTA numbers.

Figure 1

Distribution of the different alleles with different numbers of TTTAn repeats

Figure 2

Estradiol levels (pg/ml) at baseline and the 2 years follow up between the BMI groups (mean + 1 SD). P value is testing for linear trend in the three categories. Estradiol levels (pg/ml) between the three TTTAn repeats genotypes at base line and 2 years follow up per BMI groups (mean + 1 SD). P value is testing for linear trend in the three categories.

Figure 3

Change in estradiol levels (pg/ml) between the baseline and the 2 years follow up by category of weight loss in the two group of men with higher number of TTTAn repeats (X-X) and Lower number of TTTAn repeats (7-7) of the aromatase polymorphism (mean + 1 SD). The percent weight loss after follow up was divided into three categories: minimal change in weight (weight loss or gain of less than 10%) n=68, moderate weight loss (weight loss more than 10 % of the original weight but less or equal to 25%) n= 11 and severe weight loss (weight loss more than 25% of the original weight) n=37. P value is testing for linear trend in the three categories.