Comprehensive analysis of the association of EGFR, CALM3 and SMARCD1 gene polymorphisms with BMD in

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  Three genes EGFR (epidermal growth factor receptor),CALM3 (calmodulin 3,calcium-modulated protein 3,) and SMARCD1 (SWI/SNF related,matrix associated,actin dependent regulator of charomatin,subfamily d,member 1) in white women played different roles in bone and/or fat metabolism.In the population-based investigation of 870 unrelated postmenopausal white women,CALM3 polymorphisms were significantly associated with femoral neck bone mineral density (FNK BMD),hip BMD and spine BMD.Age and tobacco status also affected these BMD levels and hence were corrected for in our statistical analysis.Introduction: EGFR,CALM3 and SMARCD1 play their part in bone and/or fat metabolism,however,the correlation between polymorphisms of these three genes and body composition levels including BMD is yet undetermined.Materials and Methods: A population-based investigation of 870 white women was conducted.44 SNPs (Single Nucleotide Polymorphisms) in EGFR,CALM3 and SMARCD1 were chosen by the software of Haploview version 4.2,including those with potential functional importance.The candidate SNPs were genotyped by KASPar assay for association analysis with body composition levels at different sites.The correlation analysis was performed by the Pearson’s product-moment and Spearman rank-order test,and the family-wise error was corrected using the Wald test implement in PLINK.Results: rs12461917 in the 3′-flanking region of CALM3 gene was significantly associated with FNK BMD (P=0.001),hip BMD (P<0.001) and spine BMD (P=0.001);rs11083838 in the 5′- flanking region of CALM3 gene was associated with spine BMD (P=0.009).After adjusting for multiple comparisons,rs12461917 remained significant (Padjusted=0.033 for FNK BMD,Padjusted=0.006 for hip BMD and Padjusted=0.018 for spine BMD).Conclusions: Our data shows that polymorphisms of the CALM3 gene in white women could contribute to variation in BMD at the hip,spine,and femoral neck.
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