Wisp3 Gene Polymorphisms Associated With Postmenopausal Osteoporosis Research Late-onset Spine Epiphyseal Dysplasia Associated With Progressive Joint Department Of A Patient And His Family Wisp3 Gene Mutation Analysis

Part1Polymorphisms in the WISP3Gene Are Associated with Low Lumber Spine Bone Mineral Density in Chinese Postmenopausal Women.Introduction:The genetic determination of osteoporosis is complex and ill-defined. Wnt-1-inducible signaling pathway protein3（WISP3） participating in chondrogenesis and osteogenesis, may affect susceptibility to osteoporosis.Objective:The aim of this study is to explore the association between WISP3polymorphisms and bone phenotypes consisting of bone mineral density （BMD）, osteoporotic fractures and vertebral fractures in Chinese postmenopausal women.Methods:1570postmenopausal women of Han ethnic group were randomly selected from the Peking Vertebral Fracture （PK-VF） study in Beijing by multistage and age-stratified sampling. BMD of lumbar spine, femoral neck, and total hip were measured by dual energy X-ray absorptiometry. Fracture phenotypes were obtained by questionnaire, and vertebral fracture phenotypes were ascertained by vertebral X-ray reading. All tagging and potential functional single nucleotide polymorphisms （SNPs） in WISP3were determined by TaqMan allelic discrimination assay. Differences in BMD associated with genotype or haplotype were calculated using multiple linear regression. The odds ratio for case and control groups associated with genotype or haplotype were calculated using binary logistic regression.Results:1. BMD in lumber spine was clearly associated with rs1230345（G to T mutation）. Individuals carrying TT genotypes had a55%increased incidence of osteopenia and osteoporosis in lumber spine（OR1.554,95%CI1.116-2.165, P=0.009） and had lower BMD in femoral neck than those carrying GT （P=0.028） and GG genotypes （P=0.027）.2. Vertebral fracture was associated with rs4947163. Individuals homozygous for the minor allel had a3.8folds increased incidence of vertebral fracture （OR4.833,95%CI1.022-22.85, P=0.009）.3. Vertebral fracture was associated with rs9400518. Individuals homozygous and heterozygous for the minor allel had a57%increased incidence of vertebral fracture （OR=1.567,95%CI1.008-2.435, P=0.046）.4. BMD in lumber spine was clearly associated with haplotype b （AGCGTTA）. Individuals homozygous for this haplotype had a50%increased incidence of osteopenia and osteoporosis in lumber spine（OR=1.503,95%CI=1.048-2.157, P=0.027）.5. WISP3SNPs and haplotypes were not found association with total hip BMD.6. WISP3SNPs and haplotypes were not found association with osteoporotic fractures.Conclusion:We found that rs1230345polymorphism and lumbar spine BMD were significantly associated; rs4947163and rs9400518polymorphisms were associated with vertebral fractures. These results require confirmation in other populations and larger samples but suggest a role for the WISP3in the genetic susceptibility to osteoporosis among Chinese postmenopausal women. Part2Mutation Analysis of WISP3Gene in Two Chinese Pedigrees with Spondyloepiphyseal DysplasiaIntroduction:The WNT1-inducible signaling pathway protein3（WISP3） is a secreted matricellular protein that is involved in chondrogenesis, osteogenesis and tumorigenesis. WISP3gene mutations are associated with spondyloepiphyseal dysplasia tarda with progressive arthropathy （SEDT-PA）, an autosomal recessive genetic disease that is characterized by the swelling of multiple joints and disproportionate dwarfism.Objective:To investigate the mutation of WISP3gene in four patients with SEDT-PA and to analyze the clinical features in affected individuals..Methods:Four SEDT-PA patients from two unrelated Chinese families were recruited for this study. The clinical diagnosis was confirmed by medical history, physical examinations, laboratory results and radiological abnormalities. WISP3mutations were detected by direct DNA sequence analysis..Results:In total, four different mutations were identified, which consisted of two missense mutations, one deletion and one insertion that spanned exons3,5and6of the WISP3gene. One of the missense mutations （c.342T>G/p.C114W） and a seven-base pair frameshift deletion （c.716₇22delAAATGAG/p.E239fs*16） were novel. The other missense mutation （c.1000T>C/p. S334P） and the insertion mutation （c.866₈67insA/p.Q289fs*31） had previously been identified in Chinese patients. All four cases had a compound heterozygous status, and their parents were heterozygous carriers of these mutations.Conclusion:Clinical and molecular diagnosis was made in four patients with SEDT-PA, and novel WISP3mutations were detected。...