Nursing Department, Faculty of Nursing and Occupational Therapy, University of Extremadura, Avda de la Universidad s/n, 10003 Cáceres, Spain.
Instituto de Investigación Biosanitaria de Extremadura (INUBE), 10003 Cáceres, Spain.
Genes (Basel). 2023 Dec 2;14(12):2171. doi: 10.3390/genes14122171.
Sporadic Parkinson's disease, characterised by a decline in dopamine, usually manifests in people over 65 years of age. Although 10% of cases have a genetic (familial) basis, most PD is sporadic. Genome sequencing studies have associated several genetic variants with sporadic PD. Our aim was to analyse the promoter region of the ATG16L1 and ATG5 genes in sporadic PD patients and ethnically matched controls. Genotypes were obtained by using the Sanger method with primers designed by us. The number of haplotypes was estimated with DnaSP software, phylogeny was reconstructed in Network, and genetic divergence was explored with Seven and two haplotypes were obtained for ATG16L1 and ATG5, respectively. However, only ATG16L1 showed a significant contribution to PD and a significant excess of accumulated mutations that could influence sporadic PD disease. Of a total of seven haplotypes found, only four were unique to patients sharing the T allele (rs77820970). Recent studies using MAPT genes support the notion that the architecture of haplotypes is worthy of being considered genetically risky, as shown in our study, confirming that large-scale assessment in different populations could be relevant to understanding the role of population-specific heterogeneity. Finally, our data suggest that the architecture of certain haplotypes and ethnicity determine the risk of PD, linking haplotype variation and neurodegenerative processes.
散发性帕金森病的特征是多巴胺水平下降，通常发生在 65 岁以上的人群中。虽然 10%的病例具有遗传（家族）基础，但大多数 PD 是散发性的。基因组测序研究已经将几种遗传变异与散发性 PD 相关联。我们的目的是分析散发性 PD 患者和种族匹配对照者 ATG16L1 和 ATG5 基因的启动子区域。通过使用我们设计的引物的桑格方法获得基因型。使用 DnaSP 软件估计单倍型的数量，在 Network 中重建系统发育，并用 Seven 和两个单倍型分别获得了 ATG16L1 和 ATG5。然而，只有 ATG16L1 对 PD 有显著贡献，并且存在大量积累的突变，可能影响散发性 PD 疾病。在总共发现的七个单倍型中，只有四个是与携带 T 等位基因（rs77820970）的患者共享的。最近使用 MAPT 基因的研究支持了这样一种观点，即单倍型的结构值得从遗传上被认为是有风险的，正如我们的研究所示，这证实了在不同人群中进行大规模评估可能与理解特定人群异质性的作用有关。最后，我们的数据表明，某些单倍型和种族的结构决定了 PD 的风险，将单倍型变异与神经退行性过程联系起来。
