Analysis Of Genetic Variation Of POSTN Gene And Gene Identification Study In A Chinese Family With Spondylmetaphyseal Dysplasia

Aim:This study is divided into two parts;the first part is the study of susceptibility genes and related biochemical markers of osteoporosis:Based on the process of finding the association between the serum level of periostin with the risk of osteoporosis fracture and other bone turn overs and Bone Mineral Density(BMD);Also,exploring the association between polymorphism of Periostin(POSTN)and BMD and osteoporotic fracture in postmenopausal women.We aim to indentify the susceptible gene and unique biomarker for osteoporosis.The second part is the study of genetic mechanism of monogenetic bone disease.Through analyze the clinical manifestation and the mutant gene of a family suffering from spinal metaphyseal dysplasia type K(Spondylmetaphyseal dysplasia Kozlowski type,SMDK),we aim to find the lying pathogenesis mechanism for these rarely-seen diseases.Methods:1)in the population genetics study,we recruit 389 postmenopausal women.Bone biomarkers and other parameters were measured.Also,we used dual-energy X ray to measure BMD of all the sites for these patients.10 SNPs of the periostin gene(rs7322993,rs7338244,rs9547952,rs9547965,rs9547970,rs9603226)were genotyped 2)In the clinical study of SMDK,we analyzed the clinical and radiology and biochemical manifestations of the SMDK pedigree,and then extract DNA from their blood and healthy control groups manage to reveal the pathogenic genes.Results:In population genetic studies,compared with non-fracture patients,Patients with both vertebrate and non-vertebrate fracture tends to have a higher serum level of periostin.None association was found between SNPs,haplotype of periostin gene,and serum periostin level and bone mineral density and the risk of fracture.The proband and her mother's clinical manifestation included varus deformity,knee valgus deformity,scoliosis and metaphyseal change.Sanger sequencing revealed heterozygote mutation(c.1781G>A)in exon 11 of TRPV4 gene,which was not found in other family members and healthy controls.Conclusion:No association were found between serum periostin level and other bone turn overs.Multiple fractures group tends to have a higher serum level of periostin.Genetic polymorphisms of POSTN may not be a major variation of the serum periostin or BMD or fracture risk in postmenopausal Chinese women in Shanghai region.Also,the missense mutation c.1781G>A of the TRPV4 was the genetic pathogeny of SMDK in this study.This is the first report of TRPV4 muatation induced SMDK in China.