Structural Variants of <i>Midnolin</i>, a Genetic Risk Factor for Parkinson’s Disease, in a Yamagata Cohort

Abstract

Parkinson's disease (PD) is a common neurodegenerative disease. We previously identified Midnolin (MIDN) to be a genetic risk factor for PD in both Yamagata (Japan) and British populations. However, the scale of our previous study was not sufficient to identify MIDN structural variants in the ascertained control of Yamagata Prefecture. We, therefore, reanalyzed MIDN variants in 3021 individuals from Yamagata Prefecture to compare with that in our previous British cohort study. MIDN copy number loss was only found in two cases (0.0662%), which was a lower frequency than that (1.64%) of the previously studied British cohort. Between the Yamagata and British groups, there was significant difference for rs3746106, located in the 5′-UTR of MIDN mRNA (p 0.0003344, odds ratio 1.143), and for rs3746107, which corresponds to Ala34 (p < 2.2 10 16 , odds ratio 5.89401). This study indicates that MIDN loss is relatively rare in the general Japanese population. Considering our previous studies that the frequency of MIDN loss is high among patients with PD (10.5 and 6.55% in Yamagata and Britain, respectively), the MIDN variants are much higher genetic risk factors for PD in a Japanese population than in a British population.

Viable mutations of mouse midnolin suppress B cell malignancies

“…However, no further work on MIDN in the pancreas has been reported. Rather, several reports have focused on a putative association between MIDN gene copy number reductions and sporadic Parkinson’s disease ( Billingsley et al, 2020 ; Obara et al, 2017 , 2019 , 2020 ; Obara and Ishii, 2018 ; Sagehashi et al, 2022 ; Sato et al, 2023 ), which has been disputed ( Billingsley et al, 2020 ). Knockdown of MIDN in rat PC12 cells, a cell line derived from the adrenal gland, resulted in downregulated expression of the E3 ubiquitin ligase Parkin and the transcription factor ATF4, but the neurological significance of this is not known ( Obara et al, 2017 ).…”