Vitamin D receptor and aromatase gene interaction and bone mass in older African-American women.
Aromatization of androgens by the CYP19 gene product, aromatase, is the major source of endogenous estrogen in postmenopausal women. We determined whether an Arg(264)Cys polymorphism in the CYP19 gene is associated with bone mineral density (BMD) and bone loss in older women. Because vitamin D regulates CYP19 gene expression, we also tested for an interaction with a translation start site polymorphism in the vitamin D receptor (VDR) gene. Hip BMD was measured twice, an average of 1.9 years apart, in 100 African-American women aged > or =65 years. Neither polymorphism alone was significantly associated with BMD or bone loss. BMD measurements in women with the less frequent allele at both loci were 0.5 to 1.3 SD lower than in women with neither or only a single rare allele (P <.001 for interaction). These women also experienced more rapid hip bone loss than other women (P <.05 for interaction). We conclude that VDR and CYP19 gene polymorphisms may jointly influence bone mass and the rate of bone loss in older African-American women.
Zmuda
Joseph M
JM
Departments of Epidemiology and Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Cauley
Jane A
JA
Danielson
Michelle E
ME
Ferrell
Robert E
RE
D000368:Aged; D001141:Aromatase / Q000235:genetics*; D044383:Black People; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000033:anatomy & histology*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D018167:Receptors, Calcitriol / Q000235:genetics*; D001741:Black or African American
D018167:Receptors, Calcitriol; D004247:DNA; D001141:Aromatase