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

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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.