Abstract
BackgroundOsteoporosis, 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 JAG1 genes with bone mineral density (BMD) variation in postmenopausal Mexican-Mestizo women.MethodsFour 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.ResultsLinear 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].ConclusionsSOST 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-400) contains supplementary material, which is available to authorized users.
Highlights
Osteoporosis, a disease characterized by low bone mineral density (BMD), is an important health problem in Mexico
The quality control (QC) criteria for subject and single-nucleotide polymorphisms (SNPs) genotyping for the initial phase have been previously described [21]
Mean bone parameters were within normal range, mean Lumbar Spine (LS) BMD was 0.990 ± 0.151, which is expected given the age of study participants
Summary
Osteoporosis, a disease characterized by low bone mineral density (BMD), is an important health problem in Mexico. The MEF2C (myocyte enhancer factor 2C) gene, another member of the Wnt-signaling pathway [13], is known to play an important role in determining bone density and mediating inflammatory effects in bone [14] and Mef2C is the main transcriptional factor responsible for ECR5-dependent Sost expression in the adult skeleton of mice [15] Within this gene, rs1366594 has been associated with Femoral Neck (FN) BMD in Europeans, and with Total Hip (TH) BMD in populations from East-Asia [4,5]; while rs119510131, was found to be significantly associated with forearm BMD in the meta-analysis of 6,584 individuals of European and Mexican American descent [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
