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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.

journal_name

BMC Musculoskelet Disord

journal_title

BMC musculoskeletal disorders

authors

Velázquez-Cruz R,Jiménez-Ortega RF,Parra-Torres AY,Castillejos-López M,Patiño N,Quiterio M,Villarreal-Molina T,Salmerón J

doi

10.1186/1471-2474-15-400

subject

Has Abstract

pub_date

2014-11-28 00:00:00

pages

400

issn

1471-2474

pii

1471-2474-15-400

journal_volume

pub_type

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