title: TNFRSF11B gene haplotype and its association with bone mineral density variations in postmenopausal Mexican-Mestizo women.
abstract: OBJECTIVE
  Osteoporosis is a complex health disease characterized by low bone mineral density (BMD), which is determined by an interaction of genetics with metabolic and environmental factors. The tumor necrosis factor receptor superfamily, member 11b (TNFRSF11B) gene, has been investigated in relation to BMD. Three polymorphisms in/nearby TNFRSF11B have been associated with BMD variations in some populations. The aim of this study was to investigate the possible association among three SNPs of TNFRSF11B and their haplotypes with the presence of BMD variations in postmenopausal Mexican Mestizo women.
  
  
  METHODS
  One thousand unrelated postmenopausal women of Mexican-Mestizo ethnic origin, who attended the outpatient clinic for routine, general medical evaluation, were invited and 750 women accepted to participate in the study. A structured questionnaire for risk factors was applied and BMD was measured in total hip and lumbar spine by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Three single-nucleotide polymorphisms in TNFRSF11B gene were studied: rs4355801, rs2073618, and rs6993813. Real-time PCR allelic discrimination was used for genotyping. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype analysis was conducted.
  
  
  RESULTS
  Of the subjects, 31% had osteoporosis, 45.1% had osteopenia, and 23.9% had normal BMD. Genotype and allele distributions showed no significant differences; however, A-G-T haplotype was associated with variations in femoral neck BMD (P=0.022).
  
  
  CONCLUSIONS
  In our study population, analysis of the haplotypes of TNFRSF11B is a better genetic marker for variations in BMD.
authors.affiliation: División de Investigación Biomédica, Subdirección de Enseñanza e Investigación, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, México, D.F., Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Rojano-Mejía
authors.forename: Ramón Mauricio
authors.initials: RM
authors.lastname: Coral-Vázquez
authors.forename: Leticia Cortes
authors.initials: LC
authors.lastname: Espinosa
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Hidalgo
authors.forename: Guillermo
authors.initials: G
authors.lastname: López-Medina
authors.forename: María del Carmen Aguirre
authors.initials: Mdel C
authors.lastname: García
authors.forename: Agustín
authors.initials: A
authors.lastname: Coronel
authors.forename: Roberto
authors.initials: R
authors.lastname: Ibarra
authors.forename: Patricia
authors.initials: P
authors.lastname: Canto
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000483:Alleles; D015519:Bone Density / Q000235:genetics*; D001851:Bone Diseases, Metabolic / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005269:Femur / Q000378:metabolism*; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007962:Leukocytes; D015810:Linkage Disequilibrium; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000453:epidemiology / Q000235:genetics*; D053244:Osteoprotegerin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D015995:Prevalence; D012016:Reference Values; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D005819:Genetic Markers; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human