Analysis of association of MEF2C, SOST and JAG1 genes with bone mineral density in Mexican-Mestizo postmenopausal women

BMC Musculoskeletal Disorders

Jorge Salmerón¹  Teresa Villarreal-Molina⁴  Manuel Quiterio²  Nelly Patiño⁵  Manuel Castillejos-López³  Alma Y Parra-Torres⁶  Rogelio F Jiménez-Ortega⁶  Rafael Velázquez-Cruz⁶ 

[1] Centro de Investigación en Salud Poblacional del Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico;Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, Mexico;Unidad de Vigilancia Epidemiológica Hospitalaria, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico;Laboratorio de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica, Mexico City, Mexico;Subdirección de Desarrollo de Aplicaciones Clínicas, Instituto Nacional de Medicina Genómica, Mexico City, Mexico;Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica, Mexico City, Mexico

关键词: Mexican Women;    Genes;    JAG1;    SOST;    MEF2C;    Association study;   

Others  :  1091412
DOI  :  10.1186/1471-2474-15-400

 received in 2014-08-19, accepted in 2014-11-24,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Velázquez-Cruz et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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