title: Analysis of association of MEF2C, SOST and JAG1 genes with bone mineral density in Mexican-Mestizo postmenopausal women.
abstract: BACKGROUND
  Osteoporosis, a disease characterized by low bone mineral density (BMD), is an important health problem in Mexico. BMD is a highly heritable trait, with heritability estimates of 50-85%. Several candidate genes have been evaluated to identify those involved in BMD variation and the etiology of osteoporosis. This study investigated the possible association of single-nucleotide polymorphisms (SNPs) in the MEF2C, SOST and JAG1genes with bone mineral density (BMD) variation in postmenopausal Mexican-Mestizo women.
  
  
  METHODS
  Four hundred unrelated postmenopausal women were included in the study. Risk factors were recorded and BMD was measured in total hip, femoral neck and lumbar spine using dual-energy X-ray absorptiometry. In an initial stage, a total of twenty-five SNPs within or near SOST gene and seven SNPs in the JAG1 gene were genotyped using a GoldenGate assay. In a second stage, three MEF2C gene SNPs were also genotyped and SOST and JAG1 gene variants were validated. Real time PCR and TaqMan probes were used for genotyping.
  
  
  RESULTS
  Linear regression analyses adjusted by age, body mass index and ancestry estimates, showed that five SNPs in the SOST gene were significantly associated with BMD in total hip and femoral neck but not lumbar spine. The lowest p value was 0.0012, well below the multiple-test significance threshold (p=0.009), with mean effect size of -0.027 SD per risk allele. We did not find significant associations between BMD and MEF2C/JAG1 gene variants [rs1366594 "A" allele: β=0.001 (95% CI -0.016; 0.017), P=0.938; rs2273061 "G" allele: β=0.007 (95% CI -0.007; 0.023), p=0.409].
  
  
  CONCLUSIONS
  SOST polymorphisms may contribute to total hip and femoral neck BMD variation in Mexican postmenopausal women. Together, these and prior findings suggest that this gene may contribute to BMD variation across populations of diverse ancestry.
authors.affiliation: Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica, Mexico City, Mexico. rvelazquez@inmegen.gob.mx.
authors.forename: Rafael
authors.initials: R
authors.lastname: Velázquez-Cruz
authors.forename: Rogelio F
authors.initials: RF
authors.lastname: Jiménez-Ortega
authors.forename: Alma Y
authors.initials: AY
authors.lastname: Parra-Torres
authors.forename: Manuel
authors.initials: M
authors.lastname: Castillejos-López
authors.forename: Nelly
authors.initials: N
authors.lastname: Patiño
authors.forename: Manuel
authors.initials: M
authors.lastname: Quiterio
authors.forename: Teresa
authors.initials: T
authors.lastname: Villarreal-Molina
authors.forename: Jorge
authors.initials: J
authors.lastname: Salmerón
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015519:Bone Density / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D000072100:Jagged-1 Protein; D064326:MEF2 Transcription Factors / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008800:Mexico / Q000208:ethnology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause / Q000208:ethnology / Q000235:genetics*; D000072099:Serrate-Jagged Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D002135:Calcium-Binding Proteins; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D008565:Membrane Proteins; C422903:SOST protein, human; D000072099:Serrate-Jagged Proteins