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

ABSTRACT

Introduction: Several studies suggested a possible association between certain polymorphisms in the N-acetyl-transferase 2 (NAT2) gene (which encodes a very important enzyme involved in xenobiotic metabolism) and the risk for Parkinson’s disease (PD). As the results of studies on this issue are controversial, we conducted a systematic review and a meta-analysis of eligible studies on this putative association.

Areas covered: The authors revised the relationship between NAT2 polymorphisms and the risk of developing PD using several databases, and performed a meta-analysis using the software Meta-Disc1.1.1. In addition heterogeneity between studies was analyzed. A description of studies regarding gene-gene interactions and gene-environmental interactions involving NAT2 polymorphisms is also made.

Expert opinion: 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.

KEYWORDS:

• Parkinson’s disease
• genetics
• NAT2 polymorphisms
• meta-analysis

Article highlights

• The results of studies regarding the possible association between individual allelic SNPs in the NAT2 gene and the risk for PD were essentially negative.

• The overall results of studies addressing the possible role of acetylator phenotypes suggest a marginal increased risk for PD in slow acetylators, which was related to the heterogeneity between these studies and with the stronger associations in Chinese subjects.

• Studies exploring the putative gene-dose effect for the inferred NAT2 phenotypes did not show association between these phenotypes and the risk for PD.

• The few studies addressing the role of NAT2 polymorphisms in the specific risk for early-onset PD do not prove a clear association between early-onset PD and the acetylation status.

• Individual studies suggested gene-gene interaction of the NAT2*5 allele with the CYP2D6*10, CYP2D6*4, and UCHL1 rs5050532 polymorphisms in the risk for PD.

• Individual studies suggested a protective interaction between NAT2 rapid acetylator phenotypes and smoking in the risk for PD, while interaction of NAT2 polymorphisms with exposure to caffeine, pesticides, solvents or iron showed lack of association with PD risk.

This box summarizes key points contained in the article.

Declaration of interest

This work was supported in part by Grants PI12/00241, PI12/00324, PI15/00303 and RETICS RD12/0013/0002 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain, and GR15026 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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