NAT2 polymorphisms and risk for Parkinson’s disease: a systematic review and meta-analysis

Abstract

Despite several recent meta-analyses showing an association between several polymorphisms in genes related with detoxification mechanisms such as cytochrome P4502D6 (CYP2D6), and glutathione transferases M1 and T1 (GSTM1, and GSTT1), data on NAT2 gene polymorphisms obtained from the current meta-analysis do not support a major association with PD risk, except in Asian populations. However, data from many studies are incomplete and therefore insufficient data exists to draw definitive conclusions. Several studies suggesting gene-gene and gene-environmental factors involving NAT2 gene in PD risk await confirmation.

The Arylamine N-Acetyltransferases as Therapeutic Targets in Metabolic Diseases Associated with Mitochondrial Dysfunction

“…Several other studies, however, failed to find an association (Dupret et al, 1999;Harhangi et al, 1999;Maraganore et al, 2000;Nicholl et al, 1999;van der Walt et al, 2003). Offering a more comprehensive overview, a meta-analysis by Jiménez-Jiménez et al (2016) revealed no significant association between the NAT2 slow acetylator phenotype and Parkinson's disease within Caucasian populations. Their analysis, however, revealed a strong relationship for Asian populations.…”

“…In a pioneering study, Bandmann et al in 1997 highlighted a higher incidence of the NAT2 acetylator phenotype in patients with familial Parkinson's disease when compared to controls (Bandmann et al, 1997). Their finding spurred a series of subsequent investigations, and numerous studies have supported the association by reporting a heightened incidence of slow acetylators in cases of sporadic and early-onset Parkinson's disease across various ethnicities (Agúndez et al, 1998;Bandmann et al, 1997;Bandmann et al, 2000;Bialecka et al, 2002;Borlak and Reamon-Buettner, 2006;Chan et al, 2003;Chaudhary et al, 2005;Jiménez-Jiménez et al, 2016;Pandi et al, 2020;Singh et al, 2010;Tan et al, 2000). Several other studies, however, failed to find an association (Dupret et al, 1999;Harhangi et al, 1999;Maraganore et al, 2000;Nicholl et al, 1999;van der Walt et al, 2003).…”

“…Their analysis, however, revealed a strong relationship for Asian populations. (Jiménez-Jiménez et al, 2016). Beyond the scope of Parkinson's disease, the NAT2 genotype has emerged as a topic of study in other neurological and psychological conditions.…”

MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease

“…One such is the drugs and xenobiotics detoxification mechanisms pathways, in which a mice MPTP model of PD study showed that a polymorphism in cytochrome P450 family two subfamily D member 6 ( CYP2D6 ) caused susceptibility to PD (Jiménez-Jiménez et al, 1991 ). Following that, others have shown that some of these detoxification genes, GSTM1, GSTT1 , and NAT2 have been implicated in PD with controversial associations (Wang and Wang, 2014 ; Jiménez-Jiménez et al, 2016a ). Importantly, CYP2D6 and NAT2 genes have been shown exclusively to be associated with EOPD (Agúndez et al, 1995 ; Agundez et al, 1998 ), implying that these detoxification genes would have be suitable as EOPD biomarkers.…”

Genetics in parkinson’s disease: From better disease understanding to machine learning based precision medicine

“…The second goal of this review is to discuss the potential of machine learning approaches, which could allow to better quantify complex phenotypes and to move beyond disease understanding towards a better personalized treatment of PD in the future. While previous reviews focused on the genetic architecture of PD and discuss associated risk factors ( Billingsley et al, 2018 ), gene-specific polymorphisms ( Jiménez-Jiménez et al, 2016 ), gene-gene and gene-environment interactions ( Singh et al, 2014 ; Dunn et al, 2019 ), our review has thus a distinguishable methodological focus.…”