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.
BMC Med Genet. 2010 Jan 1;11:1. doi: 10.1186/1471-2350-11-1.
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.
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.
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).
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.
Wnt/β-连环蛋白信号通路在骨骼发育中起着重要作用。该通路的拮抗剂卷曲相关蛋白（FRZB）的多态性可能导致骨密度（BMD）的变化。在这项研究中，我们分析了 FRZB 基因型与两个较大的中国女性后代和男性后代核家族脊柱和臀部峰值 BMD 变化之间的关联。
我们从 401 个女性后代核家族中招募了 1260 名受试者，从 427 个男性后代核家族中招募了 1296 名受试者，并对整个 FRZB 基因的四个标记单核苷酸多态性（tagSNP）（rs6433993、rs409238、rs288324 和 rs4666865）进行了基因分型。由于在中国人群中，SNP rs288326 和 rs7775 的次要等位基因频率（MAF）较低，与髋关节炎相关，因此未在本研究中选择。使用定量传递不平衡检验（QTDT）分析了每个 SNP 和单倍型与女性和男性后代核家族峰值 BMD 的关联。
在女性后代核家族中，我们没有发现单个 SNP 或单倍型与脊柱或臀部峰值 BMD 之间存在关联的证据。在男性后代核家族中，无论是 SNP 还是单倍型，都没有观察到家族内关联，尽管 rs4666865 与脊柱 BMD 之间存在显著的总关联（P=0.0299）。
我们的结果表明，FRZB 的自然变异不是导致中国女性或男性峰值 BMD 可变性的主要因素。由于 FRZB 基因型在不同种族之间可能存在差异，因此需要在不同人群中进行其他研究来证实这些结果。
