Integrative Analysis Confirmed the Association between Osteoprotegerin and Osteoporosis  

整合分析证实骨保护素基因与骨质疏松症的相关性（英文）

作　　者：唐惠 朱晓炜 武龙飞 莫兴波 邓飞艳 雷署丰 

机构地区：[1]苏州大学医学部公共卫生学院遗传流行病与基因组学研究中心江苏省老年病预防与转化医学重点实验室 [2]江苏省张家港市疾病预防控制中心

出　　处：《Chinese Medical Sciences Journal》2019年第2期147-156,共10页中国医学科学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China(No.31271336)~~

摘　　要：Objective This study aimed to verify the association between osteoprotegerin gene (OPG) and its variants with osteoporosis (OP) by performing integrative analysis.Methods We used the KGG software to perform gene-based association analysis,which integrated all publicly available single-nucleotide polymorphism (SNP)-based P values and obtained an overall P value for the OPG.The significant SNPs were screened for expression quantitative trait loci (eQTLs).Meta-analysis was used to combine the associations between the variants of OPG and bone mineral density (BMD) reported in the literatures.Then we performed dual-luciferase reporter gene systems for the functional verification of the variants of OPG in vitro.Results In the gene-based association analysis,the over all P value of OPG was 6.24×10^-13 for BMD at femoral neck (FN) and 7.37×10^-17 for BMD at lumbar spine (LS),indicating the importance of OPG for OP.The publicly available eQTL database identified 5 eQTLs which exert cis-regulation effects on OPG at FN and LS.Literature searching found that rs2073617 (known as T950C) was the hot spot SNP.There were 13 relevant studies on rs2073617 besides the GEFOS-2 study identified from the PubMed.Significant differences among TT,TC and CC genotypes at FN (P= 0.047) and LS (P= 0.025) were shown by meta-analysis,demonstrating the associations between T950C polymorphism and BMD.Luciferase gene expression was significantly higher at the presence of allele C than allele T in the 293T cells (t=-9.47,P<0.01).Conclusion The integrative analysis further confirmed the importance of OPG in OP and the correlation of T950C polymorphism with BMD of OP.The strategy can be used as a reference for functional interpretation of other disease-related genes.Objective This study aimed to verify the association between osteoprotegerin gene(OPG) and its variants with osteoporosis(OP) by performing integrative analysis.Methods We used the KGG software to perform gene-based association analysis, which integrated all publicly available single-nucleotide polymorphism(SNP)-based P values and obtained an overall P value for the OPG. The significant SNPs were screened for expression quantitative trait loci(eQTLs). Meta-analysis was used to combine the associations between the variants of OPG and bone mineral density(BMD) reported in the literatures. Then we performed dual-luciferase reporter gene systems for the functional verification of the variants of OPG in vitro. Results In the gene-based association analysis, the over all P value of OPG was 6.24×10-13 for BMD at femoral neck(FN) and 7.37×10-17 for BMD at lumbar spine(LS), indicating the importance of OPG for OP. The publicly available eQTL database identified 5 eQTLs which exert cis-regulation effects on OPG at FN and LS. Literature searching found that rs2073617(known as T950 C) was the hot spot SNP. There were 13 relevant studies on rs2073617 besides the GEFOS-2 study identified from the PubMed. Significant differences among TT, TC and CC genotypes at FN(P= 0.047) and LS(P= 0.025) were shown by meta-analysis, demonstrating the associations between T950 C polymorphism and BMD. Luciferase gene expression was significantly higher at the presence of allele C than allele T in the 293 T cells(t=-9.47, P<0.01).Conclusion The integrative analysis further confirmed the importance of OPG in OP and the correlation of T950 C polymorphism with BMD of OP. The strategy can be used as a reference for functional interpretation of other disease-related genes.

关 键 词：OSTEOPROTEGERIN OSTEOPOROSIS single-nucleotide POLYMORPHISM INTEGRATIVE analysis 

分 类 号：R[医药卫生]