An association study between the genetic polymorphisms within GnRHI, LHβ and FSHβ genes and central precocious puberty in Chinese girls

Abstract

Objectives: Gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are three hypothalamic–pituitary–gonadal axis expressing hormones. They play critical roles in the onset of puberty. Here we report the relationship between the three hormones and Central Precocious Puberty (CPP) in Chinese Han girls. Methods: We analyzed the single nucleotide polymorphisms (SNPs) of 5′-flanking regions of these genes by DNA sequencing in 27 CPP samples. Then the SNPs sites were genotyped by ligase detection reaction in a total of 283 Chinese Han CPP cases and 284 matched controls. Distributions of the polymorphisms and haplotypes were calculated for statistical evaluation. Results: Nine SNPs (One in GnRHI gene: −2003 C/T; Five in LHβ gene: −1456 C/G, −1424 C/G, −238 G/A, −164 G/A and −34 T/A; Three in FSHβ gene: −1825 T/C, −261 G/T and −132 T/A.) were found. A quantitative genetic association study was made. −1825 T/C in FSHβ gene was related with CPP with a weak effect ( P = 0.025). A haplotype in the 5′-flanking region of LHβ gene was significantly associated with CPP in Chinese Han girls ( P = 8.25 × 10 −09). However, analysis software showed that none of SNP was found in the regulating control element of these genes. Conclusions: Our finding implies that the polymorphisms in the 5′-flanking regions of FSHβ gene and LHβ gene probably were related to the puberty onset time of these girls. Further studies on the polymorphisms are needed for the exact mechanism.