Association of aromatase (TTTA)n repeat polymorphisms with central precocious puberty in girls.

Abstract

OBJECTIVE: Precocious puberty is characterized by early activation of the

pituitary-gonadal axis. Oestrogen is the final key factor to start the onset of

puberty. The cytochrome P450 19A1 (CYP19A1) gene encodes an aromatase that is

responsible for the conversion of androgens to oestrogen, which is a key step in

oestrogen biosynthesis. The aim of this study was to identify CYP19A1 gene

mutations or polymorphisms in girls with central precocious puberty (CPP).

METHODS: We evaluated the frequency of allelic variants of the CYP19A1 exons and

the tetranucleotide tandem repeat (TTTA)n in intron 4 in 203 idiopathic central

precocious puberty (CPP) girls and 101 normal healthy women. RESULTS: The

genotype analysis of the CYP19A1 (TTTA)n polymorphism revealed six different

alleles ranging from seven to 13 repeats. Among the six different repeat alleles

detected in this study, the (TTTA)(1)(3) repeat allele was only detected in the

patient group and carriers of the (TTTA)(1)(3) allele were significantly

associated with an increased risk of CPP (OR = 1.509, 95% CI = 1.425-1.598, P =

0.033). Carriers of the (TTTA)(1)(3) repeat allele were significantly younger at

pubertal onset and had higher levels of oestrogen than noncarriers of the

(TTTA)(1)(3) repeat allele. Although nine polymorphisms were detected in exons of

the CYP19A1 gene, no clinical significance was observed. CONCLUSION: In this

study, carriers of a higher repeat (TTTA)(1)(3) polymorphism in intron 4 of the

CYP19A1 gene had higher levels of oestrogen. Those carrying the (TTTA)(1)(3)

repeat allele may have a higher risk of developing CPP.