NUS1'in düşük frekanslı ve nadir kodlama varyantları Parkinson hastalığının patogenezine ve fenotipine katkıda bulunur: bir vaka kontrol çalışması

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Abstract Background NUS1 has recently been identified as a candidate risk gene for Parkinson’s disease (PD), but the contribution of NUS1 rare and low-frequency variants to PD susceptibility and phenotypes is largely unknown. Methods In our case-control study, whole-exome or Sanger sequencing was performed on the subjects (4,779 cases vs. 4,442 controls) to analyze the coding sequence of NUS1 . The associations between variants and phenotypic data were analyzed using sequence kernel association test and regression models. Results A total of 13 variants were identified. Ten of them in 12 patients and one control were rare variants and three were low-frequency variants. Three rare variants (R86L, N144K, D163H) might be pathogenic. We identified a significant burden of rare NUS1 variants in PD (adjusted P=0.016). Two low-frequency variants, rs550854234 and rs539668656, were associated with PD (odds ratio = 0.76, adjusted P = 0.041; odds ratio = 2.80, adjusted P = 0.016; respectively). Analyses stratified by age at onset showed that the same two variants were associated with late-onset PD (odds ratio = 0.66, adjusted P = 0.025; odds ratio = 2.96, adjusted P = 0.025; respectively). The genotype-phenotype associations of these variants showed that patients with PD carrying rare variants, rs550854234 or rs539668656 were significantly associated with earlier onset age, emotional impairment and tremor severity. Conclusions Our study suggests that rare and low-frequency NUS1 variants play an important role in the pathogenesis and phenotype of PD. Moreover, our data will help understand the role of NUS1 plays in the pathogenesis of PD and further the development of personalized treatments for PD.

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