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

Summary: Three genes, including EGFR (epidermal growth factor receptor), CALM3 (calmodulin 3, calcium-modulated protein 3) and SMARCD1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily d member 1), play different roles in bone and/or fat metabolism in Caucasian women. In this population-based investigation of 870 unrelated postmenopausal Caucasian 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 BMD levels and were therefore corrected for in our statistical analysis.

Introduction: EGFR, CALM3 and SMARCD1 play roles in bone and/or fat metabolism. However, the correlations between the polymorphisms of these three genes and body composition levels, including BMD, remain to be determined.

Materials And Methods: A population-based investigation of 870 white women was conducted. Forty-four SNPs (single nucleotide polymorphisms) in EGFR, CALM3 and SMARCD1 were chosen by the software, including those of potential functional importance. The candidate SNPs were genotyped by the KASPar assay for an association analysis with body composition levels. The correlation analysis was assessed by the Pearson's product-moment correlation coefficient and Spearman rank-order correlation tests, and the family-wise error was corrected using the Wald test implemented in PLINK.

Results: The SNP rs12461917 in the 3'-flanking region of the 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 (P-adjusted = 0.033 for FNK BMD, P-adjusted = 0.006 for hip BMD and P-adjusted = 0.018 for spine BMD).

Conclusions: Our data show that polymorphisms of the CALM3 gene in Caucasian women may contribute to variations in the BMD of the hip, spine and femoral neck.