谷氨酰胺与骨密度、骨转换指标、wnt-7a蛋白间的孟德尔随机分析  

Causal relationship between glutamine and bone mineral density,bone turnover markers,and Wnt-7a protein:A Mendelian stochastic analysis

作　　者：陈建吉 汪静 CHEN Jianji;WANG Jing(Shenzhen Baoan Clinical College of Medicine,Guangdong Medical University,Shenzhen 518000,China)

机构地区：[1]广东医科大学深圳宝安临床医学院,广东深圳518000

出　　处：《中国骨质疏松杂志》2024年第8期1157-1163,共7页Chinese Journal of Osteoporosis

基　　金：深圳市科技创新委员会面上项目(JCYJ20210324111010028)。

摘　　要：目的使用孟德尔随机化分析(MR)方法探索谷氨酰胺(Gln)与骨密度(bone mineral density,BMD)、骨转换指标、wnt-7a蛋白之间的因果关系。方法利用全基因组关联分析(genome-wide association studies,GWAS)研究数据,暴露因素选择Gln,结局变量包括股骨颈骨密度(FN-BMD)、前臂骨密度(FA-BMD)、腰椎骨密度(LS-BMD)、全身骨密度(TB-BMD)、骨转换指标包括血清25-羟基维生素D水平[25(OH)D]、甲状旁腺素(PTH)、骨保护素(OPG)、骨钙素(BGP)、Wnt信号家族成员:wnt-7a。采用逆方差加权法、MR-Egger回归法、加权中位数方法、Simple Mode法和Weighted Mode法,并且进行异质性检验、敏感性分析和多效性分析。结果MR结果显示Gln与wnt-7a蛋白之间差异具有统计学意义,且两者关系呈正相关;Gln与FN-BMD、FA-BMD、LS-BMD、TB-BMD、25(OH)D、PTH、OPG、BGP差异均无统计学意义。本次研究的异质性检验均无异常,敏感性分析结果均显示稳健,且未发现多效性。结论该研究结果为Gln在维持骨稳态及参与成骨分化的作用及预防、治疗骨质疏松症提供了一定理论依据,说明通过摄入Gln预防和治疗骨质疏松症可能具有潜在临床意义。Objective Mendelian randomized analysis(MR)was used to explore the causal relationship between glutamine(Gln)and bone mineral density(BMD),bone turnover markers,and Wnt-7a protein.Methods Using Genome-wide association studies(GWAS)data,Gln was selected as the exposure factor.Outcome variables included femoral neck bone mineral density(FN-BMD),forearm bone mineral density(FA-BMD),lumbar bone mineral density(LS-BMD),total body bone mineral density(TB-BMD),and bone turnover indicators,including serum 25-hydroxyvitamin D levels(25(OH)D),parathyroid hormone(PTH),osteopontin(OPG),osteocalcin(BGP),and Wnt signaling family member WNT-7A.Inverse variance weighting method(IVW),MR-Egger regression method,weighted median method,simple mode method and weighted mode method were used.The heterogeneity test,sensitivity analysis,and multieffect analysis were performed.Results MR result showed that there was statistical difference between Gln and Wnt-7a protein,and the relationship between them was positive.There was no significant difference between Gln and FN-BMD,FA-BMD,LS-BMD,TB-BMD,25(OH)D,PTH,OPG,and BGP.Heterogeneity tests in this study were all normal.The sensitivity analysis result were robust,and no pleiotropy was found.Conclusion In this study,a causal relationship between Gln levels and Wnt-7a was established.The result of this study provide a theoretical basis for the role of Gln in maintaining bone homeostasis and in participating in osteogenic differentiation as well as the prevention and treatment of osteoporosis,suggesting that Gln intake may have potential clinical significance in the prevention and treatment of osteoporosis.

关 键 词：谷氨酰胺 骨质疏松症 孟德尔随机化 骨密度 骨转换指标 wnt-7a 

分 类 号：R681[医药卫生—骨科学] R153.1[医药卫生—外科学] R589[医药卫生—临床医学]