No association of the polymorphisms of the frizzled-related protein gene with peak bone mineral density in Chinese nuclear families

Abstract

BackgroundThe 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.MethodsWe 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.ResultsIn 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).ConclusionOur 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.

Association between Polymorphisms in Sclerostin, Dickkopfs and Secreted Frizzled-Related Protein Genes and Bone Mineral Density in Postmenopausal Korean Women

“…On the other hand, Lories et al [25] demonstrated no difference in the frequency of genotypes of the sFRP3 c.970C>G polymorphism between women with low-trauma hip fracture and elderly controls in a Belgian population. Moreover, Gao et al [22] have recently reported no association of the sFRP3 polymorphisms with peak BMD in the female offspring of Chinese nuclear families.…”

“…To date, several studies have investigated the relationship between bone mass and polymorphisms in these Wnt antagonist genes such as SOST, DKK1, sFRP1, sFRP3 and sFRP4 [21,22,23,24,25,26,27,28,29]. However, the results of these studies were controversial, depending on ethnicity and the type of polymorphisms or studied genes.…”

Polymorphisms in the human ALOX12 and ALOX15 genes are associated with peak bone mineral density in Chinese nuclear families

“…The recruited female offspring were healthy. The following exclusion criteria were adopted, as in our previously reported study [20][21][22], and were used to exclude individuals from this study: (1) serious residual effects from cerebral vascular disease; (2) diabetes mellitus, except for easily controlled non-insulin-dependent diabetes mellitus; (3) chronic renal disease; (4) serious chronic liver disease or alcoholism; (5) significant chronic lung disease; (6) corticosteroid therapy at pharmacological levels for >6 months; (7) treatment with anticonvulsant therapy for >6 months; (8) evidence of other metabolic or inherited bone diseases, such as hyper-or hypoparathyroidism, Paget's disease of the bone, osteomalacia, osteogenesis imperfecta; (9) rheumatoid arthritis or collagen disease; (10) recent major gastrointestinal disease within the past year such as peptic ulcers, malabsorption, chronic ulcerative colitis, regional enteritis, or any significant chronic diarrheal state; (11) significant disease in any endocrine organ that would affect bone mass; (12) hyperthyroidism; and (13) any neurological or musculoskeletal condition that could be a nongenetic cause of low bone mass.…”

Phenolic-rich extract from the Costa Rican guava (Psidium friedrichsthalianum) pulp with antioxidant and anti-inflammatory activity. Potential for COPD therapy

“…In vitro studies of human alveolar macrophages have shown that oxidative stress caused by acute cigarette smoke extract (CSE) exposure increases the release of interleukin-8 (IL-8) (Walters et al, 2005). Matrix metalloproteinases (MMPs), a family of zinc endo-peptidases, may also play an important role in COPD pathology (Babusyte et al, 2007; Haq et al, 2010). Particularly it has been described that MMP-1 is expressed in the lung of human patients with emphysema but not in normal control subjects (Imai et al, 2001).…”