| 逄淑超,闫波.自噬-溶酶体标记基因LC3B和LAMP2调控序列变异与退行性心脏瓣膜病的关联性[J].济宁医学院学报,2022,45(5):321-327 |
| 自噬-溶酶体标记基因LC3B和LAMP2调控序列变异与退行性心脏瓣膜病的关联性 |
| Association between the regulatory sequence variation of autophagy lysosome marker genes LC3B and LAMP2 and degenerative heart valve disease |
| 投稿时间：2022-09-05 |
| DOI：10.3969/j.issn.1000-9760.2022.05.004 |
| 中文关键词: 自噬-溶酶体;退行性心脏瓣膜病;LC3B基因;LAMP2基因;序列变异 |
| 英文关键词: Autophagy-lysosome;Degenerative heart valve disease;LC3B gene;LAMP2 gene;Sequence variation |
| 基金项目:国家自然科学基金(81870279,81400291) |
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| 中文摘要: |
| 目的 探索自噬-溶酶体标记基因LC3B和LAMP2调控序列变异与退行性心脏瓣膜病(DHVD)的关联性。方法 对212例DHVD患者组与390例健康对照组的自噬-溶酶体系统标记基因LC3B和LAMP2调控序列(启动子)进行统计分析。采集研究对象的外周静脉血白细胞,提取基因组DNA,应用聚合酶链反应(PCR)扩增基因LC3B和LAMP2的启动子序列,Sanger测序法直接检测序列变异。运用卡方检验对单核苷酸多态性(SNPs)进行分析,TRANSFAC数据库预测序列变异改变与启动子相结合的转录因子。结果 共发现29个序列变异,包含13个SNPs。其中,6个LC3B基因启动子序列变异仅发现于DHVD患者,1个LAMP2基因启动子序列变异只存在于DHVD女性患者,其他序列变异在健康对照组和患者组共有。对SNPs的基因型和等位基因进行卡方检验和logistic回归分析显示,rs35227715的等位基因G与DHVD相关联,是DHVD的独立危险因素,致病风险是1.36倍;rs42900基因型CC和等位基因C与DHVD存在关联,两者的致病风险均为0.56倍,具有保护性作用。利用TRANSFAC数据库预测仅在DHVD患者中发现的序列变异位点相结合的转录因子,结果表明序列变异可改变与之结合的转录因子。结论 自噬-溶酶体系统标记基因LC3B和LAMP2启动子序列变异可能影响与之结合的转录因子,改变其表达水平,引起自噬-溶酶体系统的功能失调,从而导致DHVD的发病。 |
| 英文摘要: |
| Objective To identify the relationship between the regulatory sequence variation of autophagy lysosomal marker genes LC3B and LAMP2 and degenerative heart valve disease (DHVD).Methods The promoters of LC3B and LAMP2 were analyzed in 212 patients with DHVD and 390 healthy controls.The peripheral blood leukocytes of the subjects were collected,genomic DNA was extracted,the promoter sequences of LC3B and LAMP2 were amplified by polymerase chain reaction (PCR),and the sequence variation was directly detected by Sanger sequencing.Chi square test was used to analyze single nucleotide polymorphisms (SNPs) and TRANSFAC database was used to predict the transcription factors associated with sequence variation changes and promoters.Results 29 sequence variation sites were found,including 13 SNPs.Among them,6 sequence variationsofLC3B were only found in DHVD patients,1 sequence variation of LAMP2 was only found in DHVD female patients,and other sequence variation sites were shared in the control group and the patient group.Chi square test and logistic regression analysis of genotypes and alleles of SNPs showed that the allele G of rs35227715 was associated with DHVD and was an independent risk factor for DHVD,with a disease risk of 1.36 times;the genotype CC and allele C of rs42900 were associated with DHVD,and the pathogenic risk of both was 0.56 times,with a protective effect.The transcription factors that bind to the sequence variation sites found only in DHVD patients was analyzed with the TRANSFAC database,and the results showed that the sequence variations can change the transcription factors.Conclusion The sequence variations of LC3B and LAMP2 promoter may affect the transcription factors that bind to them and change the expression levels of LC3B and LAMP2,causing the dysfunction of autophagy-lysosome system,thus leading to the pathogenesis of DHVD. |
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