DICER基因微小RNA结合区域单核苷酸多态与有氧运动能力的关联性研究

Association of DICER Genetic Polymorphisms in Micro-RNA Binding Site and Aerobic Performance Phenotypes

目的探讨DICER基因微小RNA结合区域单核苷酸多态性(single nucleotide polymorphism,SNP)与有氧运动能力表型的关联。方法选择178名大学新生进行18周的长跑训练,测定训练前后最大摄氧量绝对值(VO2max)、摄氧量相对值(rVO2max);进行跑节省化实验测定12 km/h跑速下的RE各项指标;同时测定训练前后受试者心室结构和功能相关指标。采用PCR-RFLP基因分型技术检测DICER基因rs1057035位点多态性。采用荧光素酶报告基因系统对rs1057035位点进行功能研究。结果 DICER基因rs1057035多态位点与VO2max、RE、心室结构和功能相关指标的初始值没有关联,但是与VO2max、心室结构和功能相关指标的训练敏感性有关联。长跑训练后,TC+CC基因型受试者VO2max和rVO2max变化量显著高于TT基因型者;TC+CC基因型受试者心室结构指标ESD、IVSS、PWD、LVM和LVMI变化量显著高于TT基因型者;TC+CC基因型受试者心室功能指标SV、EF变化量显著高于TT基因型者,而T变化量则显著低于TT基因型者;经协方差分析,这些差异均具有统计学意义(P<0.05)。另外,基因功能研究显示,与rs1057035位点T基因型相比,C基因型显著降低DICER基因的表达活性。结论 DICER基因rs1057035多态位点与研究对象长跑训练后有氧运动能力表型存在着关联,长跑训练后TC+CC基因型者VO2max以及部分心室结构和功能改变显著高于TT基因型者,该位点多态性可以成为人群训练敏感性的分子遗传学标记。

Objective To explore the association between single nucleotide polymorphism in DICER genetic micro - RNA binding sites and aerobic athletic ability phenotypes. Methods 178 new healthy college students were included in the present study. All subjects performed an 18 - week 5 000 m running training. The absolute value of maximum oxygen uptake （ VO2max） and the relative value of oxygen uptake （rVO2max were measured. In addition, a RE Experiment was carried out to measure all indexes of RE under the running speed of 12 km/h. At the same time, related indexes of ventricular structure and function were measured before and after the aerobic training. Polymorphisms of DICER gene rs1057035 were detected by PCR - RFLP. Luciferase reporter assay was used to study the SNP function of rs1057035 site. Results It indicates that there is no association between polymorphic site of polymorphisms of DICER gene rs1057035 and baseline levels of VO2max, RE, ventricular structure and function, while there is association between the polymorphic site and the sensibility of related indexes of VO2 ventricular structure and function to training. The carriers of C allele （TC ＋ CC genotypes） in rs1057035 of DICER gene had higher levels of VO2max, rVO2max, ventricular structure indexes including ESD, IVSS, PWD, LVM and LVMI, as well as ventricular function indexes like SV and EF and lower levels of T than carries with TI＂ genotype after 18 - week 5 000 m running program （P 〈 0.05 ）. Furthermore, covariance analysis shows that all of these differences have statis- tical significance （P 〈 0.05 ）. In addition, researches on gene function indicated rs1057035 variant C allele, leading to significantly lower expression levels compared to the T allele at the site of rs1057035. Conclusion The polymorphic site of the DICER gene rs1057035 is associated with aerobic athletic ability phenotypes. After running training VO2max and some changesin ventricular structure and function of carriers with TC ＋ CC genotype are obviously higher than that of carriers with TT genotype so that polymorphism of the site could become a sensitive molecular genetics mark for people＇s training.