PRKAA2基因SNP与HIIT干预心肺耐力及糖脂代谢敏感性的关联性研究

Study on the Correlation Between PRKAA2 Gene SNP and HIIT Intervention in Cardiopulmonary Endurance and Glucolipid Metabolism Susceptibility

目的:研究单磷酸腺苷激活的蛋白激酶α2亚基(PRKAA2)基因区的单核苷酸多态性(SNP)对高强度间歇训练(HIIT)干预后心肺耐力及糖脂代谢水平的影响,筛选HIIT干预效果敏感的候选基因标记。方法:对259名普通大学生进行为期12周的HIIT干预训练(3次/周),测定干预前后心肺功能以及糖脂代谢指标。提取受试者基因组DNA进行基因分型,Plink软件分析干预前后指标变化值与基因型之间的关联。对多位点相关联的表型,进行多基因遗传易感性评分(GPS),分析GPS与表型之间的相关性;分析多位点可能形成的单体型与指标变化量的关联性。全基因组关联分析(GWAS)平台检索有关联性多态位点的特征,3D SNP在线软件预测位点可能的生物学功能。结果:1)PRKAA2基因区rs706468与HIIT训练后最大摄氧量(VO2max)、肺通气量(VE)变化之间显著相关(P<0.05),AA纯合子为优势基因型;rs3738565与HIIT训练后低密度脂蛋白(LDL)变化之间显著相关(P<0.05),G等位基因为优势基因型;rs17848596与HIIT训练后肺通气量变化之间显著相关(P<0.05),T等位基因为优势基因型。2)rs706468、rs17848596两个位点的总基因分数与肺通气量变化之间显著相关(R^(2)=0.043,P<0.05),回归方程为:△VE=6.144+1.092×GPS_(W)。3)多位点可能形成的单体型与所有指标变化量无显著性关联。4)软件预测显示,rs706468位点具有较强的基因表达增强作用,rs3738565位点在物种间的保守性较强。结论:1)PRKAA2基因SNP位点rs706468-AA、rs3738565-G、rs17848596-T基因型与HIIT干预后训练效果相关联,可作为预测HIIT训练效果的遗传分子标记候选位点。2)多基因遗传易感性评分对HIIT训练后肺通气量指标训练敏感性的评价效果良好,可解释4.3%的肺通气量增加。3)多位点SNP之间未形成与训练敏感性相关的单体型,其生物学机制尚需进一步实验研究。

To investigate effects of the Homo sapiens protein kinase,AMP-activated,alpha 2 catalytic subunit(PRKAA2) gene single nucleotide polymorphism(SNP) on cardiorespiratory endurance,glucose and lipid metabolism after high-intensity interval training(HIIT) intervention.The aim is to screen relevant susceptibilited potential genetic markers.Methods:A total of 259 college students were trained by HIIT intervention for 12 weeks(3 times/week).Indexes of cardiopulmonary function and glucose and lipid metabolism were measured before and after HIIT intervention.Genomic DNA was extracted for genotyping,and the relationship between the index changes and genotype before and after intervention was analyzed by Plink software.Polygenic genetic predisposition scoring(GPS) was performed on phenotypes associated with multiple loci,and the correlation between GPS and phenotypes was analyzed.The association between possible haplotypes formed at multiple loci and indicator variations was analyzed.The genome-wide association analysis(GWAS) platform searched for the features of the associated polymorphic sites,and the 3D SNP online software predictd the possible biological functions of the sites.Results:1) There was a significant correlation between rs706468 of PRKAA2 gene region and VO2max and,ventilation volume(VE) variation after HIIT training(P<0.05),AA homozygote was the dominant genotype;a significant correlation between rs3738565and low-density lipoprotein(LDL) change after HIIT training(P<0.05),G allele was the dominant genotype;and a significant correlation between rs17848596 and VE after HIIT training(P<0.05),T allele was the dominant genotype.2)The total gene score of rs706468 and rs17848596 was significantly correlated with VE variation(P<0.05).The regression equation:△VE=6.144+1.092GPSW.3) The possible haplotypes formed by multiple sites were not significantly associated with the variation of all indicators.4) The software prediction showed that the rs706468 site has a strong gene expression enhancement effect,and the rs3738565 site was strongly conserved among species.Conclusions:1) PRKAA2 SNP Loci rs706468-AA,rs3738565-G,rs17848596-T have positive correlation on the effect of HIIT intervention training,which could be used as potential genetic molecular markers to predict the effect of HIIT training.2) The GPS was has a good evaluation effect on the training sensitivity of VE after HIIT training,which accounted for 4.3% of the increase in VE.3) No haplotypes related to training sensitivity were formed between multilocus SNP,and the biological mechanism need further experimental investigation.