Genetic control of pubertal onset : role of polymorphism of LH/CG and GnRH receptor gene

我们研究了促性腺激素释放激素受体（GnRHR）、促黄体生成素/绒毛膜促性腺激素受体（LHCGR）和促卵泡激素受体（FSHR）基因单核苷酸多态性（snp）与青春期发病的关系。研究对象为青春期早发和青春期晚发者（n=20和14）。这些snp的信息来自日本单核苷酸多态性数据库JSNP网站。GnRHR基因中有6个snp， LHCGR基因中有7个snp， FSHR基因中有25个snp。在对照组（n=16）中对每个snp进行基因分型。选择2个GnRHR基因的snp、2个LHCGR基因的snp和4个FSHR基因的snp进行单倍型分析，这些snp之间的相关性不强。GnRHR基因的单倍型频率在对照组与青春期早发和青春期晚发组存在差异。单倍型频率在青春期早发者和青春期晚发者之间无显著差异，LHCGR基因也无显著差异。FSHR基因的单倍型频率IMS-JST012841和IMS-JST022161在对照组和青春期开始延迟的被试中存在差异，但差异很小，不能作为区分青春期开始时间的有效工具。结论：病例对照法未发现GnRHR、LHCGR和FSHR基因与青春期发病有明确关联。

We investigated the association of single nucleotide polymorphisms (SNPs) in gonadotropin releasing hormone receptor (GnRHR), luteinizing hormone/choriogonadotropin receptor (LHCGR), and follicle stimulating hormone receptor (FSHR) genes with pubertal onset. Subjects are those with early and delayed pubertal onset (n=20 and 14, respectively). Information on the SNPs were obtained from the web site of JSNP, a database of Japanese Single Nucleotide Polymorphisms. There are 6 SNPs in the GnRHR, 7 SNPs in the LHCGR, and 25 SNPs in the FSHR gene. Each SNPs were genotyped in the controls (n=16). Two SNPs in the GnRHR gene, 2 SNPs in the LHCGR gene, and 4 SNPs in the FSHR gene, not strongly associated with each others, were selected for haplotype analysis.Haplotype frequencies of the GnRHR gene in the controls are different from those in the subjects with early and delayed pubertal onset. But there are no differences of haplotype frequencies between in the subjects with early and delayed pubertal onset, and also in the LHCGR gene. Haplotype frequencies n the FSHR gene, IMS-JST012841 and IMS-JST022161, were different in the controls and in the subjects with delayed pubertal onset, but the difference was small and did not give us a useful tool for differentiating the timing of pubertal onset.In conclusion, no evidence for definete association of GnRHR, LHCGR, and FSHR gene with pubertal onset was detected using case-control methods.