NEB基因多态性与汉族成年人12周抗阻运动干预前后肌肉质量变化值的关联研究  

Association Between Nebulin Polymorphisms and the Changes in Muscle Mass after 12 Weeks of Resistance Training in Han Adults

作　　者：顾壮壮 胡扬[1] 何子红[2] 杨晓琳[1] 梅涛[1] 晏冰[1] 段佳妍 梁丽娟[1] 张之豪 王亚琦 李燕春[1] Gu Zhuangzhuang;Hu Yang;He Zihong;Yang Xiaolin;Mei Tao;Yan Bing;Duan Jiayan;Liang Lijuan;Zhang Zhihao;Wang Yaqi;Li Yanchun(Beijing Sport University,Beijing 100084,China;China Institute of Sport Science,Beijing 100061,China)

机构地区：[1]北京体育大学,北京100084 [2]国家体育总局体育科学研究所,北京100061

出　　处：《中国运动医学杂志》2023年第4期257-265,共9页Chinese Journal of Sports Medicine

基　　金：国家重点研发计划(2018YFC2000602)。

摘　　要：目的:通过分析伴肌动蛋白(nebulin,NEB)基因多态性与12周抗阻运动干预后全身肌肉质量变化值的关联性,筛选NEB基因中可以作为预测抗阻运动干预引起的全身肌肉质量变化值个体差异的遗传分子标记。方法:共招募169名汉族大学生(男85人,女84人),年龄21.68±1.95岁,并在12周运动干预前后采用双能X线测试受试者的全身肌肉质量,抽取静脉血5ml,使用TIANGEN DNA提取试剂盒进行DNA提取;通过illumina CGA芯片技术完成基因分型;采用PLINK1.9、haploview4.1、SAS 9.3进行数据统计分析。基于HaploReg-v4.1在线分析工具,依据ENCODE TF数据库和GETxv6数据库验证阳性SNP的生物学功能。基于阳性SNP构建遗传预测分数模型(genetic predisposition scores,GPS),并采用逐步回归分析方式计算出GPS的解释度。结果:(1)NEB基因的3个SNP(rs2288200、rs7597735、rs73967578)与全身肌肉质量变化值存在关联(P<0.05)。(2)生物学分析发现,3个SNP可影响多个转录因子结合及基因表达,其中rs2288200影响GCNF、HDAC2_disc5、Irf_known3、Irf_known9、STAT_disc3与该区域DNA的结合;rs7597735影响Gfi1、HNF4、Mef2与该区域DNA结合,且该位点影响RIF1基因在13种组织中的表达;rs73967578影响转录调节因子DMRT2、PHA-4/FoxA、Foxd3、Mef2、Pou2f2、Pou3f2与该区域DNA的结合。(3)基于3个SNP构建GPS评分模型,经逐步回归发现GPS评分的R2值为0.0308(P=0.0020),GPS评分大于24.1的受试者肌肉质量变化值显著高于评分低于24.1的受试者(P=0.0050)。结论:NEB基因rs2288200、rs7597735、rs73967578多态性位点可以作为汉族成年人抗阻运动干预后全身肌肉质量变化值的遗传分子标记,基于NEB基因的3个SNP建立的GPS可以解释全身肌肉质量变化值个体差异的3.08%。Objective To analyze the association between nebulin(NEB)polymorphisms and changes in muscle mass after 12 weeks of resistance training,and identify genetic markers in the NEB gene that can be used to predict individual variations in whole body muscle mass changes after such intervention.Methods A total of 169 college students(85 males and 84 females)of the Han nationality and aged 21.68±1.95 years were recruited.The dual-energy X-ray absorptiometry(DEXA)was employed to measure the whole body muscle mass before and after 12-week exercise intervention.Then,five ml of venous blood was collected,and DNA was extracted using the TIANGEN DNA extraction kit.Genotyping was performed using the Illumina CGA chips.Statistical analysis of the data was carried out using PLINK1.9,haploview4.1,and SAS 9.3.Based on the HaploReg-v4.1,the biological function of identified SNPs was verified using the ENCODE TF and GETxv6 databases.Then,a genetic prediction score(GPS)model was constructed,and its interpretability was calculated using the stepwise regression analysis.Results Three SNPs of the NEB genes(rs11680579,rs7597735 and rs73967578)exhibited significant associations with changes in whole muscle mass(P0.05).Moreover,the bioinformatics analysis revealed that three SNPs affected the binding of multiple transcription factors and therefore the expression of associated genes.To be more specific,rs2288200 had an effect on the binding of GCNF and HDAC2_disc5,Irf_known3,Irf_known9,STAT_disc3 to DNA,while the Rs7597735 affected the binding of Gfi1,HNF4,and Mef2 to DNA,and the expression of RIF1 gene in 13 tissues.Moreover,Rs73967578 could have an impact on the binding of transcription regulators DMRT2,PHA-4/FoxA,Foxd3,Mef2,Pou2f2 and Pou3f2 to DNA.Based on these three SNPs,a GPS scoring model was constructed.Meanwhile,stepwise regression analysis indicated that the R2value of the GPS score was 0.0308(P=0.0020)and individuals with a GPS score greater than 24.1 had significantly higher muscle mass changes compared to those with a GPS scor

关 键 词：NEB基因 抗阻运动干预 遗传预测分数 关联分析 

分 类 号：R685[医药卫生—骨科学]