2004 Fiscal Year Final Research Report Summary

Relationship of genetic diversity of hypothalamo-pituitary-gonadal axis and puberatal onset

Research Project

Project/Area Number	15591077
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Pediatrics
Research Institution	Asahikawa Medical College
Principal Investigator	ITO Yoshiya Asahikawa Medical College, Pediatrics, Associate Professor, 医学部, 助教授 (70241437)
Co-Investigator(Kenkyū-buntansha)	MAKITA Yoshio Asahikawa Medical College, Pediatrics, Instructor, 医学部, 助手 (20271778) MUKAI Tokuo Asahikawa Medical College, Pediatrics, Instructor, 医学部, 助手 (50374799)
Project Period (FY)	2003 – 2004
Keywords	Pubertal onset / genetic control / SNP / Haplotype / steroidogenesis
Research Abstract	In order to investigate the association of genetic background of hypothalamo-pituitary-gonadal axis to pubertal onset, we selected appropriate single nucleotide polymorphisms (SNPs) in gonadotropin releasing hormone (GnRH), luteinizing hormone, (LH), follicle stimulating hormone (FSH), HSD17B3, CYP3A4, CYP17, CYP1B1, and CYP1A2 genes. Information on SNPs of those genes are collected from two SNP databases (JSNP : http://snp.ims.u-tokyo.ac.jp/ and Ensemble Project : http://www.ensembl.org/Homo_sapiens/). There are 10 SNPs in the GNRH1 gene, 4 SNPs in the LHB gene, 6 SNPs in the FSHB gene, 12 SNPs in the HSD17B3 gene, 7 SNPs in the CYP1A2 gene, 8 SNPs in the CYP3A4 gene, 6 SNPs in the CYP1B1 gene, 8 SNPs in the CYP3A4 gene, and 12 SNPs in the CYP17A1 gene. We constructed forward and backward primer to amplify the SNPs and analyze alleies using Primer 3 (http://www-genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi). Then, we calculated r2 and D' in each SNPs in the gene to select candidate SNPs for haplotype analysis. We decided to select 3 SNPs in the GnRH gene, 3 SNPs in the LHB gene, 4 SNPs in the FSHB gene, 9 SNPs in the HSD17B3 gene, 8 SNPS in the CYP17gene, 5 SNPs in the CYP1B1 gene, and 5 SNPS in the CYP1A2 gene. We could not select any SNPs in the CYP 3A4 gene because of high correlation between each SNPs. Using these SNPs in the genes, we have to construct haplotype to clarify genetic control of pubertal onset.