AMPK及其下游基因与有氧运动能力相关分子标记筛选及功能研究
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摘要
研究目的：通过分析AMPK及其下游基因多态性在我国北方汉族长跑运动员中的分布特征,筛选与长跑能力相关的分子标记；通过与长跑训练前后生理指标的关联分析,筛选与长跑训练敏感性相关的分子标记；通过研究多态位点的生物功能,阐明多态位点不同基因型在表达调控上的作用,为解释分子标记与有氧运动能力的关系提供实验依据。
研究方法：1、利用MALDI-TOF技术和Genescan技术解析AMPKα2、MEF2A、PFK2、TORC2、ACC-β、CPT-1β、HSL等基因17个SNP、2个STR多态位点在长跑运动员和普通人中的分布特征,分析基因多态性与长跑能力的相关性；2、利用MALDI-TOF技术解析AMPKα2、CPT-1β基因9个SNP位点在男性青年中的分布特征,分析基因多态性与长跑训练前后生理指标变化的关联性;3、利用基因重组、细胞转染等分子生物学方法研究Glut4基因启动子区与有氧耐力关联的rs5418位点携带不同等位基因的启动子对报告基因表达活性的影响。
结果与结论：1、基因多态性与长跑能力相关性分析结果显示：(1)AMPKα2基因rs2796516位点G等位基因可能是优秀女子长跑运动员的分子标记；rs2746342-rs11206889位点AC单体型可能是男子优秀长跑运动员的分子标记,CC单体型可能是女子5/10km运动员的分子标记。(2)HSL基因第六内含子处(CA)n重复多态当以4重复次数为分割点划分短链和长链等位基因进行比较时,LL基因型可能是5/10km运动员的分子标记。2、基因多态性与长跑训练敏感性指标的相关性分析结果显示：(1)AMPKα2基因：rs1418442的AA型、rs11206889的CC型与部分单体型的LVMI指标,以及部分单体型的IVSD指标和部分单体型150W时SVI指标的训练敏感性最高。(2)CPT-1β基因：rs131758的AA型的HR/RE.PWS指标、rs131758-rs470117(AT)单体型安静时SVI、T、COI指标训练敏感性最高。以上基因型/单体型可能是长跑训练敏感性分子标记。3、rs5418位点携带A等位基因的重组载体中报告基因相对活性显著高于携带G等位基因的重组载体,说明其部分生物学活性在于不同等位基因能显著改变启动子活性,从而影响Glut4基因表达活性
Objects:In this study, the molecular markers associated with long-distance running ability were screened through analyzing the distribution of AMPK and its downstream genes'polymorphisms in Han of northern China long-distance runners. The molecular markers associated with long-distance running training sensitivity were screened through analyzing the relationship between genotype and the changes of physiological indexes after long-distance running training. To clarify the function of different allele contribute to gene expression, the biological function of polymorphisms loci was investigated. It may provided experimental evidence for evaluate the relationship between molecular markers and aerobic endurance capability.
Methods:1. Genetic distribution for 17 SNP and 2 STR locos of AMPK a 2、MEF2A、PFK2、TORC2、ACC-β、CPT-1βand HSL genes in long-distance runners and controls were determined based on MALDI-TOF and Genescan. The relativity between gene locus and long distance running ability was analyzed.2. Genetic distribution for 9 SNP locus of AMPKα2、CPT-1βgenes in young men were determined by MALDI-TOF. The relativity between gene locus and the changes of physiological indexes after long-distance running training were analyzed.3. The molecular biological methods such as gene recombination and cell transfection were used to research the effects of Glut4 promoter carrying different allele in rs5418 contributes to the expression activity of reporter gene.
Results and conclusions:1. Polymorphisms and their association with long distance performance suggests, (1)For AMPKα2, the G allele (rs2796516) might be served as molecular marker of elite female long distance runners. AC haplotype (rs2746342-rs11206889) might be used as molecular marker of elite male International long distance runners. CC haplotype (rs2746342-rs11206889) might be used as molecular marker of elite female 5/10km long distance runners. (2)Comparing short and long chain allele split by 4, the LL genotype of (CA)n of HSLi6 might be a molecular marker of elite 5/10km long distance runners.2.Polymorphisms and their association with training sensityvity suggests, (1)for AMPK a 2, the locus with higher lever in training sensitivity include the genotype of AA(rs1418442)、CC(rs11206889) and some haplotypes responded to LVMI, certain genotypes responded to IVSD and special genotypes responded to SVI/150W. (2)For CPT-1β, the genotype of AA(rs131758) had a higher lever in the training sensitivity responded to HR/RE and PWS. the haplotype of AT(rs131758-rs470117) had a higher lever in the training sensitivity responded to SVI、T and COI in rest state. Above genotypes/haplotypes might be used as molecular markers of long-distance running training sensitivity.3. is a functional molecular marker of aerobic endurance capability. The relative activity of reporter gene carrying A allele of rs5418 in promoter of Glut4 in recombinant vector is significantly higher than that of G allele. The biological activity of this loci is that different alleles can alter promoter activity significantly, thus affecting the activity of Glut4 gene expression.
研究方法：1、利用MALDI-TOF技术和Genescan技术解析AMPKα2、MEF2A、PFK2、TORC2、ACC-β、CPT-1β、HSL等基因17个SNP、2个STR多态位点在长跑运动员和普通人中的分布特征,分析基因多态性与长跑能力的相关性；2、利用MALDI-TOF技术解析AMPKα2、CPT-1β基因9个SNP位点在男性青年中的分布特征,分析基因多态性与长跑训练前后生理指标变化的关联性;3、利用基因重组、细胞转染等分子生物学方法研究Glut4基因启动子区与有氧耐力关联的rs5418位点携带不同等位基因的启动子对报告基因表达活性的影响。
结果与结论：1、基因多态性与长跑能力相关性分析结果显示：(1)AMPKα2基因rs2796516位点G等位基因可能是优秀女子长跑运动员的分子标记；rs2746342-rs11206889位点AC单体型可能是男子优秀长跑运动员的分子标记,CC单体型可能是女子5/10km运动员的分子标记。(2)HSL基因第六内含子处(CA)n重复多态当以4重复次数为分割点划分短链和长链等位基因进行比较时,LL基因型可能是5/10km运动员的分子标记。2、基因多态性与长跑训练敏感性指标的相关性分析结果显示：(1)AMPKα2基因：rs1418442的AA型、rs11206889的CC型与部分单体型的LVMI指标,以及部分单体型的IVSD指标和部分单体型150W时SVI指标的训练敏感性最高。(2)CPT-1β基因：rs131758的AA型的HR/RE.PWS指标、rs131758-rs470117(AT)单体型安静时SVI、T、COI指标训练敏感性最高。以上基因型/单体型可能是长跑训练敏感性分子标记。3、rs5418位点携带A等位基因的重组载体中报告基因相对活性显著高于携带G等位基因的重组载体,说明其部分生物学活性在于不同等位基因能显著改变启动子活性,从而影响Glut4基因表达活性
Objects:In this study, the molecular markers associated with long-distance running ability were screened through analyzing the distribution of AMPK and its downstream genes'polymorphisms in Han of northern China long-distance runners. The molecular markers associated with long-distance running training sensitivity were screened through analyzing the relationship between genotype and the changes of physiological indexes after long-distance running training. To clarify the function of different allele contribute to gene expression, the biological function of polymorphisms loci was investigated. It may provided experimental evidence for evaluate the relationship between molecular markers and aerobic endurance capability.
Methods:1. Genetic distribution for 17 SNP and 2 STR locos of AMPK a 2、MEF2A、PFK2、TORC2、ACC-β、CPT-1βand HSL genes in long-distance runners and controls were determined based on MALDI-TOF and Genescan. The relativity between gene locus and long distance running ability was analyzed.2. Genetic distribution for 9 SNP locus of AMPKα2、CPT-1βgenes in young men were determined by MALDI-TOF. The relativity between gene locus and the changes of physiological indexes after long-distance running training were analyzed.3. The molecular biological methods such as gene recombination and cell transfection were used to research the effects of Glut4 promoter carrying different allele in rs5418 contributes to the expression activity of reporter gene.
Results and conclusions:1. Polymorphisms and their association with long distance performance suggests, (1)For AMPKα2, the G allele (rs2796516) might be served as molecular marker of elite female long distance runners. AC haplotype (rs2746342-rs11206889) might be used as molecular marker of elite male International long distance runners. CC haplotype (rs2746342-rs11206889) might be used as molecular marker of elite female 5/10km long distance runners. (2)Comparing short and long chain allele split by 4, the LL genotype of (CA)n of HSLi6 might be a molecular marker of elite 5/10km long distance runners.2.Polymorphisms and their association with training sensityvity suggests, (1)for AMPK a 2, the locus with higher lever in training sensitivity include the genotype of AA(rs1418442)、CC(rs11206889) and some haplotypes responded to LVMI, certain genotypes responded to IVSD and special genotypes responded to SVI/150W. (2)For CPT-1β, the genotype of AA(rs131758) had a higher lever in the training sensitivity responded to HR/RE and PWS. the haplotype of AT(rs131758-rs470117) had a higher lever in the training sensitivity responded to SVI、T and COI in rest state. Above genotypes/haplotypes might be used as molecular markers of long-distance running training sensitivity.3. is a functional molecular marker of aerobic endurance capability. The relative activity of reporter gene carrying A allele of rs5418 in promoter of Glut4 in recombinant vector is significantly higher than that of G allele. The biological activity of this loci is that different alleles can alter promoter activity significantly, thus affecting the activity of Glut4 gene expression.
引文
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