KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease
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Le résumé fourni par la source
Background: Selective loss of dopaminergic neurons and diminished putamen gray matter volume (GMV) represents a central feature of Parkinson’s disease (PD). Recent studies have reported specific effects of kinectin 1 gene (KTN1) variants on the putamen GMV. Objective: To examine the relationship of KTN1 variants, KTN1 mRNA expression in the putamen and substantia nigra pars compacta (SNc), putamen GMV, and PD. Methods: We examined the associations between PD and a total of 1847 imputed KTN1 single nucleotide polymorphisms (SNPs) in one discovery sample [2,000 subjects with PD vs. 1,986 healthy controls (HC)], and confirmed the nominally-significant associations (p<0.05) in two replication samples (900 PD vs. 867 HC, and 940 PD vs. 801 HC, respectively). The regulatory effects of risk variants on the KTN1 mRNA expression in putamen and SNc and the putamen GMV were tested. We also quantified the expression levels of KTN1 mRNA in the putamen and/or SNc for comparison between PD and HC in five independent cohorts. Results: Six replicable and two non-replicable KTN1-PD associations were identified (0.009≤p≤0.049). The major alleles of five SNPs, including rs12880292, rs8017172, rs17253792, rs945270 and rs4144657, significantly increased risk for PD (0.020≤p≤0.049) and putamen GMVs (19.08≤β≤60.38; 2.82≤Z≤15.03; 5.0×10-51≤p≤0.018). The risk alleles of five SNPs, including rs8017172, rs17253792, rs945270, rs4144657 and rs1188184 also significantly increased the KTN1 mRNA expression in the putamen or SNc (0.021≤p≤0.046). The KTN1 mRNA was abundant in the putamen and/or SNc across five independent cohorts and differentially expressed in the SNc between PD and HC in one cohort (p=0.047). Conclusion: There was a consistent, significant, replicable, and robust positive relationship among the KTN1 variants, PD risk, KTN1 mRNA expression in putamen, and putamen volumes, and a modest relation between PD risk and KTN1 mRNA expression in SNc, suggesting that KTN1 may play a functional role in the development of PD.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease
- Date Crossref
- 23/06/2020
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Deyang Stomatological Hospital pays non établi dans la noticeÉtablissement de santé
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Shanghai Jiao Tong University Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Tongren Hospital pays non établi dans la noticeÉtablissement de santé
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Deyang Stomatological Hospital, Department of Neurology — Shanghai Jiao Tong University et Tongren Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.