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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

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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.

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Acknowledgments

This work was supported by grants from the Consejo Nacional de Ciencia y Tecnología (CONACYT: SALUD-2008-C01-87331 and partially supported by SALUD-2010-C01-139795 and INMEGEN/CI/26/2010).

The authors would like to thank all the study participants for their participation in this study.

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Authors and Affiliations

  1. Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica, México, D.F., C.P. 14610, México

    Rafael Velázquez-Cruz

  2. Laboratorio de Inmunogenómica y Enfermedades Metabolicas, Instituto Nacional de Medicina Genómica, México, D.F., México

    Humberto García-Ortiz & Lorena Orozco

  3. Unidad de Vigilancia Epidemiológica Hospitalaria, Instituto Nacional de Enfermedades Respiratorias, México, D.F., México

    Manuel Castillejos-López

  4. Centro de Investigación en Salud Poblacional, Instituto Nacional de salud Pública, Cuernavaca, Morelos, México

    Manuel Quiterio

  5. Servicio de Genética, Instituto Nacional de Rehabilitación, México, D.F., México

    Margarita Valdés-Flores

  6. Laboratorio de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica, México, D.F., México

    Teresa Villarreal-Molina

  7. Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, México

    Jorge Salmerón

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  1. Rafael Velázquez-Cruz
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  2. Humberto García-Ortiz
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  3. Manuel Castillejos-López
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  5. Margarita Valdés-Flores
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  6. Lorena Orozco
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  7. Teresa Villarreal-Molina
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  8. Jorge Salmerón
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Correspondence to Rafael Velázquez-Cruz.

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Velázquez-Cruz, R., García-Ortiz, H., Castillejos-López, M. et al. 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. AGE 36, 9635 (2014). https://doi.org/10.1007/s11357-014-9635-2

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