title: The ESR2 AluI gene polymorphism is associated with bone mineral density in postmenopausal women.
abstract: Multiple factors may contribute to the pathogenesis of postmenopausal osteoporosis including environmental, life-style and genetic factors. Common variants in ESR2 gene encoding for ER-beta, highly expressed in bone tissue, have recently been proposed as candidates for affecting bone phenotype at the population level, particularly in postmenopausal women. In this study, we examined the genetic background at ESR2 AluI (rs4986938, 1730G>A) locus in 89 osteopenic, postmenopausal women (age range 49-56 years) together with BMD at lumbar spine and femoral neck sites as well as variations in plasma levels of bone metabolism and turnover markers. Genotyping for ESR2 G1730A polymorphism showed that the frequency of A mutated allele accounted for 0.4 in our cohort of postmenopausal women; moreover, the GA1730 heterozygous individuals were the most represented (50.6%) compared with GG (37.8%) and AA homozygous ones (14.6%). A regression analysis showed that lumbar spine BMD values were significantly associated with both ESR2 AA1730 genotype (p=0.044) and time since the onset of menopause (p=0.031), while no significant association was detected between biochemical markers and genetic background. Interestingly, 85% of patients with AA1730 genotype presented the smallest lumbar spine BMD values. These findings first indicate a worsening effect of ESR2 AluI polymorphism on lumbar spine BMD reduction in postmenopause, suggesting that the detection of this ESR2 variant should be recommended in postmenopausal women, particularly in populations with a high prevalence of ESR2 AA1730 homozygous genotype.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Via C Valeria, Policlinico G Martino, 98124 Messina, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Currò
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Angela
authors.initials: A
authors.lastname: Alibrandi
authors.forename: Nadia
authors.initials: N
authors.lastname: Ferlazzo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Condello
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Elena B
authors.initials: EB
authors.lastname: Adamo
authors.forename: Marco
authors.initials: M
authors.lastname: Atteritano
authors.forename: Rosario
authors.initials: R
authors.lastname: D'Anna
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ientile
authors.forename: Daniela
authors.initials: D
authors.lastname: Caccamo
mesh_terms: D000483:Alleles; D015519:Bone Density / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause
chemical_list: D047629:Estrogen Receptor beta