Background: Evidence suggests that precocious pubarche (PP) girls may have higher risk of developing polycystic ovary syndrome (PCOS) at later ages. Vitamin D receptor (VDR) gene polymorphisms have been implicated in the risk of diabetes and PCOS, but little is known about the role of VDR in PP.
Aim: To assess the frequencies of VDR gene ApaI, TaqI, BsmI, and FokI polymorphisms and to determine whether these variants are associated with sex hormone concentrations in patients with PP and controls from southern Brazil.
Subjects and methods: Blood was collected from 36 girls with PP and 197 controls for genotyping of BsmI and FokI polymorphisms using real-time PCR and of ApaI e TaqI polymorphisms using restriction fragment length polymorphism. Hormone levels were also determined.
Results: Genotype GG of the ApaI single nucleotide polymorphism (SNP) was more frequent in PP (30.6%) than in controls (16.2%) [odds ratio (OR): 2.269; confidence interval 95% (95%CI): 1.015-5.076; p=0.042]. This genotype was also associated with lower estradiol [35.30 (14.80-50.48) pg/ml vs 12.22 (6.49-23.69) pg/ml; p=0.025] and total testosterone levels (0.52 (0.39-0.84) ng/ml vs 0.20 (0.11-0.47) ng/ml; p=0.005) as compared with the TT + TG genotypes in girls with PP. The distribution of TaqI, BsmI, and Fokl SNP was similar in PP and controls, and no association was found between these polymorphisms and sex steroid levels.
Conclusions: The ApaI SNP of the VDR gene was associated with PP in the studied population and may modulate ovarian steroid secretion in these girls.
Keywords: Adrenarche; precocious pubarche; single nucleotide polymorphism; steroid hormones; vitamin D; vitamin D receptor.