目的 研究Atg7内含子区rs11706903单核苷酸多态性与帕金森病的关系。方法 2013年1月至2017年3月,收集130例帕金森病患者(病例组)和同期109例健康体检者(对照组)血样,采用聚合酶链反应-限制性片段长度多态性分析方法检测Atg7 rs11706903基因多态性。结果 rs11706903位点各基因型病例组基因型频率AA 10.00%、AC 52.31%、CC 37.69%,等位基因频率A 36.15%、C 63.85%;对照组基因型频率AA 7.34%、AC 49.54%、CC 43.12%,等位基因频率A 32.11%、C 67.89%。两组间无显著性差异(χ2<1.001, P>0.05)。结论 Atg7内含子区rs11706903单核苷酸多态性与帕金森病可能无关。
Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) of rs11706903, intron region of Atg7, and Parkinson's disease (PD).Methods From January, 2013 to March, 2017, 130 PD patients and 109 healthy subjects were recruited and collected the blood samples. SNPs of rs11706903 were detected with polymerase chain reaction restriction fragment length polymorphism.Results For the patients, the genotype frequencies of rs11706903 were AA 10.00%, AC 52.31% and CC 37.69%; and allele frequencies were A 36.15% and C 63.85%. For the healthy controls, the genotype frequencies of rs11706903 were AA 7.34%, AC 49.54% and CC 43.12%; and allele frequencies were A 32.11% and C 67.89%. There was no significant difference in frequencies of genetypes and alleles beteen two groups (χ2<1.001, P>0.05).Conclusion There might be no relationship between SNPs of Atg7 intron region rs11706903 and PD.
[1] Gan-Or Z, Dion PA, Rouleau GA. Genetic perspective on the role of the Autophagy-Lysosome Pathway in Parkinson disease [J]. Autophagy, 2015, 11(9): 1443-1457.
[2] Schulz JB. Mechanisms of neurodegeneration in idiopathic Parkinson's disease [J]. Parkinsonism Relat Disord, 2007, 13(Suppl 3): S306-S308.
[3] Reichmann H. Clinical criteria for the diagnosis of Parkinson's disease [J]. Neurodegener Dis, 2010, 7(5): 284-290.
[4] Koch JC, Bitow F, Haack J, et al. Alpha-Synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons [J]. Cell Death Dis, 2015, 6(7): e1811.
[5] Lynch-Day MA, Mao K, Wang K, et al. The role of autophagy in Parkinson's disease [J]. Cold Spring Harb Perspect Med, 2012, 2(4): a009357.
[6] Vuppalapati KK, Bouderlique T, Newton PT, et al. Targeted deletion of autophagy genes Atg5 or Atg7 in the chondrocytes promotes caspase-dependent cell death and leads to mild growth retardation [J]. J Bone Miner Res, 2015, 30(12): 2249-2261.
[7] Komatsu M, Waguri S, Chiba T, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice [J]. Nature, 2006, 441(7095): 880-884.
[8] Crews L, Spencer B, Desplats P, et al. Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of α-synucleinopathy [J]. PLoS One, 2010, 5(2): e9313.
[9] Yao TP. The role of ubiquitin in autophagy-dependent protein aggregate processing [J]. Genes Cancer, 2010, 1(7): 779-786.
[10] Stefanis L. α-synuclein in Parkinson's disease [J]. Cold Spring Harb Perspect Med, 2012, 2(2): a009399.
[11] Cao Y, Cai J, Li X, et al. Autophagy governs erythroid differentiation both in vitro and in vivo [J]. Hematology, 2016, 21(4): 225-233.
[12] Kaiser SE, Mao K, Taherbhoy AM, et al. Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures [J]. Nat Struct Mol Biol, 2012, 19(12): 1242-1249.
[13] Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing [J]. EMBO J, 2000, 19(21): 5720-5728.
[14] Molaei S, Roudkenar MH, Amiri F, et al. Down-regulation of the autophagy gene, ATG7, protects bone marrow-derived mesenchymal stem cells from stressful conditions [J]. Blood Res, 2015, 50(2): 80-86.
[15] Cai Z, Zeng W, Tao K, et al. Chaperone-mediated?autophagy: roles in neuroprotection [J]. Neurosci Bull, 2015, 31(4): 452-458.
[16] Friedman LG, Lachenmayer ML, Wang J, et al. Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotespresynaptic accumulation of α-synuclein and LRRK2 in the brain [J]. J Neurosci, 2012, 32(22): 7585-7593.
[17] Juhász G, Erdi B, Sass M, et al. Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in drosophila [J]. Genes Dev, 2007, 21(23): 3061-3066.
[18] Ahmed I, Liang Y, Schools S, et al. Development and characterization of a new Parkinson's disease model resulting from impaired autophagy [J]. J Neurosci, 2012, 32(46): 16503- 16509.
[19] Pattison JS, Osinska H, Robbins J, et al. Atg7 induces basal autophagy and rescues autophagic deficiency in CryABR120G cardiomyocytes [J]. Circ Res, 2011, 109(2): 151-160.
[20] Cookson MR. Cellular functions of LRRK2 implicate vesicular trafficking pathways in Parkinson's disease [J]. Biochem Soc Trans, 2016, 44(6): 1603-1610.
[21] Manzoni C. The LRRK2-macroautophagy axis and its relevance to Parkinson's disease [J]. Biochem Soc Trans, 2017, 45(1): 155-162.
[22] Guerreiro PS, Huang Y, Gysbers A, et al. LRRK2 interactions with α-synuclein in Parkinson's disease brains and in cell models [J]. J Mol Med (Berl), 2013, 91(4): 513-522.
[23] Chen D, Pang S, Feng X, et al. Genetic analysis of the ATG7 gene promoter in sporadic Parkinson's disease [J]. Neurosci Lett, 2013, 534: 193-198.
[24] 赵西耀,何芳梅. PSMA6基因rs17458312位点多态性与脑梗死的相关性研究[J]. 中国康复理论与实践, 2015, 21(9): 1091-1094.
[25] 赵西耀,何芳梅. PSMA6基因rs1048990位点多态性与动脉粥样硬化性脑梗死的相关性分析[J]. 温州医科大学学报, 2016, 46(2): 97-101.
