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


BACKGROUND
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.


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.
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha Hunan, 410008, China.
Qiu-Hong
QH
Zhou
Osteoporosis Research Center, Creighton University Medical Center, Creighton University, 601 N 30th ST, Suite 4820, Omaha, Nebraska, 68131, United States of America; Department of Biostatistics & Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, 70112, United States of America.
Lan-Juan
LJ
Zhao
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha Hunan, 410008, China.
Ping
P
Wang
Tulane University School of Medicine, New Orleans, Louisiana, 70112, United States of America.
Rhamee
R
Badr
Osteoporosis Research Center, Creighton University Medical Center, Creighton University, 601 N 30th ST, Suite 4820, Omaha, Nebraska, 68131, United States of America.
Xiao-Jing
XJ
Xu
Osteoporosis Research Center, Creighton University Medical Center, Creighton University, 601 N 30th ST, Suite 4820, Omaha, Nebraska, 68131, United States of America.
Feng-Xiao
FX
Bu
Osteoporosis Research Center, Creighton University Medical Center, Creighton University, 601 N 30th ST, Suite 4820, Omaha, Nebraska, 68131, United States of America.
Joan
J
Lappe
Osteoporosis Research Center, Creighton University Medical Center, Creighton University, 601 N 30th ST, Suite 4820, Omaha, Nebraska, 68131, United States of America.
Robert
R
Recker
Osteoporosis Research Center, Creighton University Medical Center, Creighton University, 601 N 30th ST, Suite 4820, Omaha, Nebraska, 68131, United States of America; Department of Biostatistics & Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, 70112, United States of America.
Yu
Y
Zhou
Osteoporosis Research Center, Creighton University Medical Center, Creighton University, 601 N 30th ST, Suite 4820, Omaha, Nebraska, 68131, United States of America; Department of Biostatistics & Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, 70112, United States of America.
An
A
Ye
Osteoporosis Research Center, Creighton University Medical Center, Creighton University, 601 N 30th ST, Suite 4820, Omaha, Nebraska, 68131, United States of America; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha Hunan, 410008, China.
Bo-Ting
BT
Zhou
D001823:Body Composition / Q000235:genetics; D015519:Bone Density / Q000235:genetics*; D002147:Calmodulin / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics
D002147:Calmodulin; D002868:Chromosomal Proteins, Non-Histone; C109786:SMARCD1 protein, human; D014157:Transcription Factors; C512478:EGFR protein, human; D066246:ErbB Receptors