title: WNT3A gene polymorphisms are associated with bone mineral density variation in postmenopausal mestizo women of an urban Mexican population: findings of a pathway-based high-density single nucleotide screening.
abstract: Osteoporosis (OP) is a common skeletal disorder characterized by low bone mineral density (BMD) and is a common health problem in Mexico. To date, few genes affecting BMD variation in the Mexican population have been identified. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) located in genes of the Wnt pathway with BMD variation at various skeletal sites in a cohort of postmenopausal Mexican women. A total of 121 SNPs in or near 15 Wnt signaling pathway genes and 96 ancestry informative markers were genotyped in 425 postmenopausal women using the Illumina GoldenGate microarray SNP genotyping method. BMD was measured by dual-energy X-ray absorptiometry in total hip, femoral neck, Ward's triangle, and lumbar spine. Associations were tested by linear regression for quantitative traits adjusting for possible confounding factors. SNP rs752107 in WNT3A was strongly associated with decreased total hip BMD showing the highest significance under the recessive model (P = 0.00012). This SNP is predicted to disrupt a binding site for microRNA-149. In addition, a polymorphism of the Wnt antagonist DKK2 was associated with BMD in femoral neck under a recessive model (P = 0.009). Several LRP4, LRP5, and LRP6 gene variants showed site-specific associations with BMD. In conclusion, this is the first report associating Wnt pathway gene variants with BMD in the Mexican population.
authors.affiliation: Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica, México, D.F., C.P. 14610, México, rvelazquez@inmegen.gob.mx.
authors.forename: Rafael
authors.initials: R
authors.lastname: Velázquez-Cruz
authors.forename: Humberto
authors.initials: H
authors.lastname: García-Ortiz
authors.forename: Manuel
authors.initials: M
authors.lastname: Castillejos-López
authors.forename: Manuel
authors.initials: M
authors.lastname: Quiterio
authors.forename: Margarita
authors.initials: M
authors.lastname: Valdés-Flores
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
authors.forename: Teresa
authors.initials: T
authors.lastname: Villarreal-Molina
authors.forename: Jorge
authors.initials: J
authors.lastname: Salmerón
mesh_terms: D015502:Absorptiometry, Photon; D000483:Alleles; D015519:Bone Density / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015994:Incidence; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D017698:Postmenopause; D014505:Urban Population; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C555510:WNT3A protein, human; D060509:Wnt3A Protein; D004247:DNA