线粒体Cytb基因单核苷酸多态性在不同运动群体中的分布及应激相关指标表达
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摘要
线粒体是组织细胞能量代谢的主要场所,线粒体基因组(mtDNA)的单核苷酸多态性(Single Nucleotide Polymorphism,SNP)可改变呼吸链功能进而影响组织细胞的代谢与功能。此外相关报道显示细胞色素b(Cytochrome b,Cytb)的SNP突变与肌病及多种代谢相关。多重PCR技术是近年发展起来的一项以传统PCR为基础的,高精度的多通量基因分析的技术,可同时准确测定数十种基因突变或表达情况。为探索线粒体基因突变及基因表达与运动应激的相关性,本研究以1196名省级运动队以上运动员及116名健康查体人员为研究对象,通过采集外周血样品,提取全血DNA和总RNA,采用多重PCR法进行SNP检测,进行炎性细胞因子基因表达的检测;并检测样本血清中应激相关蛋白、酶类指标及与能量代谢相关的糖、脂类,建立运动员一般生理生化指标基本参数,探索运动相关基因与代谢的差异,为线粒体基因多态性在代谢中的潜在作用和应激损伤相关研究提供了科学数据和初步探讨。主要研究内容如下:
1.在测序基础上寻找中国人群Cytb基因的SNP分型,研究Cytb基因SNP在不同运动项群的运动员中的分布。测序后得到13个差异位点,发现Cytb14766[T/C]位点的SNP在运动员中分布、15930[A/G]在不同运动项群中分布差异明显;
2.建立并优化了GeXP多重基因表达检测方法,发现炎性因子在运动员中表达发生改变,提示机体应激状态可调控基因表达。利用生物信息学将IL-8、TNF-α和IL-4三个指标综合分析,可有效鉴别运动员与非运动员的差异;
3.发现血脂、血糖类代谢指标在不同SNP分型中呈现差异,说明人体代谢水平与遗传因素有关,通过SNP分析可了解运动员生理代谢水平与训练能力的差异;
4.Cytb 14766[T/C]位点的SNP可能由于改变了氨基酸序列从而改变了蛋白功能,更利于ATP的释放,因而可能与调节肌肉力量通路有关,而15930[A/G]可能与线粒体在高强度运动中能量的无氧代谢作用有关。
5.证明了长期运动对机体糖代谢和血脂类代谢有影响,建立了运动员部分生化与分子生物学参数的基础数据。
小结:
应用高通量SNP检测技术检测线粒体中基因SNP和基于多重PCR技术的基因表达(mRNA)检测技术建立了稳定的技术平台,建立了不同项群运动员分子生物学与生化指标的基本参数,及运动应激的评价手段,为相应技术的临床应用奠定了基础。
Mitochondria has key role in energy metabolism of all cells and tissues. Mitochondrial DNA single nucleotide polymorphisms(SNPs) change the functioning of the electron transport chain(ETC),which lead to energy metabolism changes.Cytochrome b(Cytb) on mitochondrial DNA is reported to be closely linked with myopathy,which indicates the effect of Cytb SNP on muscle energy metabolism.Multi-PCR has been developed recently based on traditional PCR;it is a high precision and high output technology in detecting less than 30 gene expression in one PCR test.To investigate the relationship on mitochondria Cytb SNP and stress related gene expression during exercise,this study tests 1196 elite athletes and 116 un-athlete healthy controls' blood samples for Cytb SNP and stress related gene expression by DNA and mRNA with multi-PCR,and serum proteins,lipids and Apoliprotein is also tested.From this study,we have formed basic data of athletes and explored metabolism changes caused by exercise which can give us clues for protection from stress and possible role of mitochondrial SNP to metabolism.The details are:
1.Sequncing of Cytb is used to identify SNP among Chinese people.13 Cytb polymorphism was found.14766[T/C]and 15930[A/G]was found statistical difference between athletes and un-athlete healthy controls.
2.Multi-PCR systems were founded and optimized using a GeXP technic.Some cytokines was changing in athletes;IL-8,IL-8,TNF-αand IL-4 could used for multi-analysis to differentiate athletes and un-athlete healthy controls which involved in stress conditions.
3.Different lipids and glucose were found in different SNP alleles,which indicate genetic factors were related with metabolism.SNP analysis could help to better understand difference of athletes' metabolism levels and capability.
4.Cytb 14766[T/C]polymorphism might involved in regulation of strength; 15930[A/G]polymorphism might affect energy metabolism in highly oxygendeficiency exercise.
5.Long-term exercises were proved to affect lipids and glucose levels.Part of blood chemicals levels and physiological markers was set as basic data.
In conclusion,high output gene detection platforms of SNP and gene expression with multi-PCR are set in this study.Part of blood chemicals levels and physiological markers was set as basic data in different type of athletes,with evaluation of exercise related stress.This study can help to supplement basal research of clinical diagnosis.
1.在测序基础上寻找中国人群Cytb基因的SNP分型,研究Cytb基因SNP在不同运动项群的运动员中的分布。测序后得到13个差异位点,发现Cytb14766[T/C]位点的SNP在运动员中分布、15930[A/G]在不同运动项群中分布差异明显;
2.建立并优化了GeXP多重基因表达检测方法,发现炎性因子在运动员中表达发生改变,提示机体应激状态可调控基因表达。利用生物信息学将IL-8、TNF-α和IL-4三个指标综合分析,可有效鉴别运动员与非运动员的差异;
3.发现血脂、血糖类代谢指标在不同SNP分型中呈现差异,说明人体代谢水平与遗传因素有关,通过SNP分析可了解运动员生理代谢水平与训练能力的差异;
4.Cytb 14766[T/C]位点的SNP可能由于改变了氨基酸序列从而改变了蛋白功能,更利于ATP的释放,因而可能与调节肌肉力量通路有关,而15930[A/G]可能与线粒体在高强度运动中能量的无氧代谢作用有关。
5.证明了长期运动对机体糖代谢和血脂类代谢有影响,建立了运动员部分生化与分子生物学参数的基础数据。
小结:
应用高通量SNP检测技术检测线粒体中基因SNP和基于多重PCR技术的基因表达(mRNA)检测技术建立了稳定的技术平台,建立了不同项群运动员分子生物学与生化指标的基本参数,及运动应激的评价手段,为相应技术的临床应用奠定了基础。
Mitochondria has key role in energy metabolism of all cells and tissues. Mitochondrial DNA single nucleotide polymorphisms(SNPs) change the functioning of the electron transport chain(ETC),which lead to energy metabolism changes.Cytochrome b(Cytb) on mitochondrial DNA is reported to be closely linked with myopathy,which indicates the effect of Cytb SNP on muscle energy metabolism.Multi-PCR has been developed recently based on traditional PCR;it is a high precision and high output technology in detecting less than 30 gene expression in one PCR test.To investigate the relationship on mitochondria Cytb SNP and stress related gene expression during exercise,this study tests 1196 elite athletes and 116 un-athlete healthy controls' blood samples for Cytb SNP and stress related gene expression by DNA and mRNA with multi-PCR,and serum proteins,lipids and Apoliprotein is also tested.From this study,we have formed basic data of athletes and explored metabolism changes caused by exercise which can give us clues for protection from stress and possible role of mitochondrial SNP to metabolism.The details are:
1.Sequncing of Cytb is used to identify SNP among Chinese people.13 Cytb polymorphism was found.14766[T/C]and 15930[A/G]was found statistical difference between athletes and un-athlete healthy controls.
2.Multi-PCR systems were founded and optimized using a GeXP technic.Some cytokines was changing in athletes;IL-8,IL-8,TNF-αand IL-4 could used for multi-analysis to differentiate athletes and un-athlete healthy controls which involved in stress conditions.
3.Different lipids and glucose were found in different SNP alleles,which indicate genetic factors were related with metabolism.SNP analysis could help to better understand difference of athletes' metabolism levels and capability.
4.Cytb 14766[T/C]polymorphism might involved in regulation of strength; 15930[A/G]polymorphism might affect energy metabolism in highly oxygendeficiency exercise.
5.Long-term exercises were proved to affect lipids and glucose levels.Part of blood chemicals levels and physiological markers was set as basic data.
In conclusion,high output gene detection platforms of SNP and gene expression with multi-PCR are set in this study.Part of blood chemicals levels and physiological markers was set as basic data in different type of athletes,with evaluation of exercise related stress.This study can help to supplement basal research of clinical diagnosis.
引文
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