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Human Molecular Genetics Advance Access published online on June 16, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl155
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© The Author 2006. Published by Oxford University Press. All rights reserved
Received May 17, 2006
Revised June 13, 2006
Accepted June 13, 2006

Article

Polymorphisms of Estrogen-Biosynthesis Genes CYP 17 and CYP19 may influence Age at Menarche: a Genetic Association Study in Caucasian Females

Yan Guo 1, Dong-Hai Xiong 2, Tie-Lin Yang 1, Yan-Fang Guo 3, Robert R. Recker 2, and Hong-Wen Deng 4 *

1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P R China
2 Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, NE 68131, USA
3 Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, P R China
4 The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P R China; Department of Orthopedic Surgery, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108; Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, P R China; University of Missouri/Kansas City, School of Medicine, Department of Basic Medical Science, 2411 Holmes Street Room: M3-CO3, Kansas City, Missouri 64108-2792

* To whom correspondence should be addressed.
Hong-Wen Deng, E-mail: dengh{at}umkc.edu


  Abstract

Variation in age at menarche (AAM) is known to be substantially influenced by genetic factors, but the true causal genes remain largely unidentified. Since the increased amplitude of estrogen exposure of tissues initiates the onset of menarche, the genes involved in estrogen biosynthesis are natural candidate genes underlying AAM. Our study aimed to identify whether the CYP 17 and CYP19, the two key genes involved in the biosynthesis of estrogen, are associated with AAM variation in 1048 females from 354 Caucasian nuclear families. We genotyped 38 SNPs and established the LD (linkage disequilibrium) blocks and haplotype structures which covered the full transcript length of those two genes. The family-based and population-based statistical analyses were used to test for associations with all of the single SNPs and haplotypes. Both methods consistently detected significant associations for five SNPs of CYP19 with AAM. Haplotype analyses corroborated our single-SNP results by showing that the haplotypes in block 1 were highly significant to AAM in population-based analyses. However, we could not find any association of CYP17 with AAM. Our study is the first to suggest the important effect of CYP19 on AAM variation in Caucasian females. It will be valuable to replicate and confirm these findings in other independent studies, aiming at eventually finding the hidden genetic mechanisms underlying the variation in AAM.


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