title: Association study of the oestrogen signalling pathway genes in relation to age at natural menopause.
abstract: Genetic factors play a significant role in influencing the variation of age at natural menopause (AANM). Estrogen receptor beta (ESR2), is an important factor in the mechanism of action of estrogen, while the aromatase gene (CYP19) and the 17-alpha-hydroxylase gene (CYP17) are involved in the biosynthesis of estrogen. We tested whether polymorphisms of ESR2, CYP19 and CYP17 genes are associated with AANM in Caucasian females. A total of 52 SNPs (17 for ESR2, 28 for CYP19, and 7 for CYP17) were successfully genotyped for 229 Caucasian women having experienced natural menopause. Comprehensive statistical analyses focusing on the association of these genes with AANM were conducted. The effects of age, height and age at menarche on AANM were adjusted when conducting association analyses. We found that six SNPs (2, 6-7, 9, 13 and 16) within ESR2 were not significantly associated with AANM after Bonferroni correction. However, two blocks of ESR2 were associated with AANM. For CYP19, two SNPs (24 and 27) were nominally associated with AANM. No significant association was observed between CYP17 and AANM. Our results suggest that genetic variation in the ESR2 and CYP19 genes may influence the variation in AANM in Caucasian women.
authors.affiliation: 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, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: He
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Xiong
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000367:Age Factors; D001141:Aromatase / Q000235:genetics; D001483:Base Sequence; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008593:Menopause / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D047629:Estrogen Receptor beta; D004967:Estrogens; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase