Background of study: Twin studies have shown that age at menarche may be subject to hereditary influences but the specific determinants are unknown. Estrogens are known to have an important role in menarche. Since aromatase is responsible enzyme for the conversion of androgens to estrogens, the aromatase (CYP19) gene could be a candidate gene for the regulation of menarche. The aim of this study was to investigate the possible association of the CYP19(TTTA)n polymorphism with age at menarche.
Methods: We studied 130 healthy adolescent females from a closed community in northwestern Greece. Information on menarche was obtained through interviews. The body mass index (BMI) was recorded. The CYP19(TTTA)n polymorphism was genotyped.
Results: The mean age at menarche was 12.9±1.2 years and the BMI=19.8±2.3 kg/m2. Genotype analysis revealed 5 CYP19(TTTA)n alleles containing 711 TTTA repeats. As short allele (S) was characterized the allele with <9 TTTA and as long allele (L) the allele with ≥9 TTTA repeats. The subjects were subdivided into two groups based on median age of menarche. Group 1 included girls with menarche <13 years and group 2 girls with menarche ≥13 years. Among girls with SS genotypes, 52.9% were in group 1 compared with 47.1% in group 2 and among girl with SL and LL genotypes 45% were in group 1 compared with 55% in group 2. This difference was due to the allele with 7 TTTA repeats, since 65.5% of the girls being homozygous for this allele were in group 1 compared with 43.1% of the girls with other genotypes (P=0.03). Furthermore, homozygous girls for the allele with 7 TTTA repeats had earlier menarche (12.45±0.9 years) than girls carrying other genotypes (13.04±1.2 years; P=0.02). This difference was independent of BMI.
Conclusion: There is evidence for a genetic contribution of the CYP19 gene to the age at menarche.
03 - 07 May 2008
European Society of Endocrinology