title: CYP1A1 and CYP1B1 polymorphisms and their association with estradiol and estrogen metabolites in women who are premenopausal and perimenopausal.
abstract: The purpose of this study was to relate measured concentrations of estradiol (E2) and the urinary estrogen metabolites 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1) to single nucleotide polymorphisms (SNPs) from CYP1A1 and CYP1B1, the primary genes involved in estrogen catabolism. We investigated the association of 4 CYP1A1 SNPs (CYP1A1 rs4646903, CYP1A1 rs1531163, CYP1A1 rs2606345, and CYP1A1 rs1048943) and 2 CYP1B1 SNPs (CYP1B1 rs162555 and CYP1B1 rs1056836) to circulating serum E2 concentrations and the urinary estrogen metabolites 2-OHE1 and 16alpha-OHE1. The associations were evaluated in 1,340 participants of 4 racial/ethnic groups from the Study of Women's Health Across the Nation (SWAN) who were premenopausal and perimenopausal. There was substantial variation in the allele frequencies of the SNPs for African American and Caucasian women. There was, however, remarkable comparability between Chinese and Japanese women; their CYP1A1 and CYP1B1 allele frequencies differed by only < or =11%. There was significant variation in E2 concentrations by genotype within racial/ethnic group for CYP1A1 rs2606345. In particular, Japanese women with the CC genotype had lower E2 concentrations than did Japanese women with the AC genotype. Chinese women with the CC genotype had higher 2-OHE1 concentrations than did Chinese women with the AC genotype. Further, African American women with the CC genotype had higher 16alpha-OHE1 concentrations than did those with other genotypes. CYP1A1 rs2606345 may play an important role in estrogen metabolism in women who are premenopausal and perimenopausal.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48104, USA. mfsowers@umich.edu
authors.forename: MaryFran R
authors.initials: MR
authors.lastname: Sowers
authors.forename: Angela L
authors.initials: AL
authors.lastname: Wilson
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Kardia
authors.forename: Jian
authors.initials: J
authors.lastname: Chu
authors.forename: Daniel S
authors.initials: DS
authors.lastname: McConnell
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism*; D004967:Estrogens / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015394:Molecular Structure; D047648:Perimenopause / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017697:Premenopause / Q000502:physiology*; D044469:Racial Groups
chemical_list: D004967:Estrogens; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1