Objectives: To explore the association of KISS1, LIN28B, vitamin D receptor (VDR), and estrogen receptor α (ERα) gene polymorphisms and the risk of early with fast puberty (EFP) risk, and with hormone levels in EFP cases, in Chinese girls.
Methods: The analysis was based on the data of 141 girls with EFP and 152 girls without EFP. Clinical features were documented, and all SNP genotyping was conducted using SNaPshot method. Statistical analysis was performed to assess the association of the SNPs with EFP risk, and with hormone levels in EFP cases.
Results: There was a significant association between rs7759938-C polymorphism in the LIN28B gene and the risk for EFP in the recessive (TT + CT vs. CC) model (p = 0.040). Remarkably, rs5780218-delA polymorphism in the KISS1 gene and rs2234693-C polymorphism in the ERα gene were significantly associated with peak LH (luteinizing hormone) levels (p = 0.008, 0.045) and peak LH/FSH (follicle-stimulating hormone) ratio (p = 0.007, 0.006). Additionally, on 7 of the 8 variant loci the alleles associated with increased levels of both peak LH levels and peak LH/FSH ratio in EFP cases were also associated with increased CPP risk.
Conclusions: Our findings indicate that rs7759938-C polymorphism in the LIN28B gene might have a protective effect on EFP susceptibility. The most striking findings of this study is that, rs5780218-delA polymorphism in the KISS1 gene and rs2234693-C polymorphism in the ERα gene influenced levels of GnRH-stimulated peak LH and LH/FSH ratio, and in general CPP risk genes might also contributes to the abnormality of hormonal levels in EFP.
Keywords: Early and fast puberty; KISS1; LIN28B; estrogen receptor α; gene polymorphisms; hypothalamic-pituitary-gonadal axis; vitamin D receptor.