No association of the polymorphisms of the frizzled-related protein gene with peak bone mineral density in Chinese nuclear families.
BACKGROUND
The Wnt/beta-catenin signaling pathway plays an important role in skeletal development. Polymorphisms of frizzled-related protein (FRZB), an antagonist of this pathway, may generate variations in bone mineral density (BMD). In this study, we analyzed the association between FRZB genotypes and peak BMD variation in the spines and hips of two relatively large samples of Chinese female-offspring and male-offspring nuclear families.


METHODS
We recruited 1,260 subjects from 401 female-offspring nuclear families and 1,296 subjects from 427 male-offspring nuclear families and genotyped four tagging single nucleotide polymorphisms (tagSNPs) (rs6433993, rs409238, rs288324, and rs4666865) spanning the entire FRZB gene. The SNPs rs288326 and rs7775, which are associated with hip osteoarthritis, were not selected in this study because of their low minor allele frequencies (MAFs) in Chinese people. The quantitative transmission disequilibrium test (QTDT) was used to analyze the association between each SNP and haplotype with peak BMD in female- and male-offspring nuclear families.


RESULTS
In the female-offspring nuclear families, we found no evidence of an association between either single SNPs or haplotypes and peak BMD in the spine or hip. In the male-offspring nuclear families, no within-family association was observed for either SNPs or haplotypes, although a significant total association was found between rs4666865 and spine BMD (P = 0.0299).


CONCLUSIONS
Our results suggest that natural variation in FRZB is not a major contributor to the observed variability in peak BMD in either Chinese females or males. Because ethnic differences in the FRZB genotypes may exist, other studies in different population are required to confirm such results.
Gao
Gao
G
The Department of Osteoporosis, Metableic Bone Disease and Genetics Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Rd, Shanghai 200233, PR China. gaogao1023@126.com
Zhang
Zhen-Lin
ZL
He
Jin-Wei
JW
Zhang
Hao
H
Yue
Hua
H
Hu
Wei-Wei
WW
Gu
Jie-Mei
JM
Fu
Wen-Zhen
WZ
Hu
Yun-Qiu
YQ
Li
Miao
M
Liu
Yu-Juan
YJ
Yu
Jin-Bo
JB
D000328:Adult; D000368:Aged; D000483:Alleles; D015519:Bone Density / Q000235:genetics*; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000099274:Frizzled-Related Proteins
D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D000099274:Frizzled-Related Proteins