Association of aromatase (TTTAn) repeat polymorphism length and the relationship between obesity and decreased sperm concentration

BACKGROUND Obesity in men is associated with low sperm count, however, this finding is inconsistent. Here, we describe length of the short tandem repeat aromatase (CYP19A1) polymorphism and its relationship to increased weight and sperm count. METHODS A cohort of 215 men was recruited from the community and BMI, hormone levels and sperm parameters were determined at enrollment. Men (196) were genotyped for length of the tetranucleotide TTTA repeats polymorphism (TTTAn), defined as short (S ≤ 7 repeats) or long (L > 7 repeats). Genotypes were categorized using allele combinations as ‘low repeats’ = S–S, or ‘high repeats’ = S–L/L–L. Weight and sperm parameters were examined in relation to size of TTTAn repeat. RESULTS Mean (±SD) age was 29.8 ± 8.6 years and mean BMI was 25.6 ± 4.6 kg/m2. Men with high repeats had higher estradiol (E2) levels (98.0 ± 33.36 pmol/l) than men with low repeats (85.9 ± 26.61 pmol/l; P= 0.026). Lower FSH levels tended to be present in men with high repeats versus men with low repeats (P= 0.052). After stratification by genotype, a negative correlation between BMI and sperm count (Pearson's coefficient = 0.406) was seen only among men with high repeats (P= 0.019). Only men with high repeats exhibited increased E2 with increased weight. A decrease in testosterone: E2 ratio with increasing BMI was more pronounced in men with high versus low, repeats (R2 = 0.436 versus 0.281). CONCLUSIONS Higher TTTA repeat numbers (>7 repeats) in the aromatase gene are associated with a negative relationship between obesity and sperm count. The effect of obesity on E2 and sperm count appears to be absent in men with low (≤7) repeats.