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

<p><b>Introduction</b>: Several studies suggested a possible association between certain polymorphisms in the <i>N-acetyl-transferase 2</i> (<i>NAT2</i>) 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.</p> <p><b>Areas covered</b>: The authors revised the relationship between <i>NAT2</i> polymorphisms and the risk of developing PD using several databases, and performed a meta-analysis using the software <i>Meta-Disc1.1.1</i>. In addition heterogeneity between studies was analyzed. A description of studies regarding gene-gene interactions and gene-environmental interactions involving <i>NAT2</i> polymorphisms is also made.</p> <p><b>Expert opinion</b>: Despite several recent meta-analyses showing an association between several polymorphisms in genes related with detoxification mechanisms such <i>as cytochrome</i> P4502D6 (<i>CYP2D6</i>), and <i>glutathione transferases M1</i> and <i>T1</i> (<i>GSTM1</i>, and <i>GSTT1</i>), data on <i>NAT2</i> 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 <i>NAT2</i> gene in PD risk await confirmation.</p

<i>MAPT rs1052553</i> genotypes and allelic variants of patients with essential tremor and healthy volunteers distributed by gender.

<p>The values in each cell represent: number (percentage; 95% confidence intervals).</p

<i>MAPT rs1052553</i> genotypes and allelic variants of patients with essential tremor (ET) and healthy volunteers.

<p>The values in each cell represent: number (percentage; 95% confidence intervals).</p

Case-control studies on <i>VDR</i> rs731236 (Taq1) and risk for MS (NA = data not available).

<p>Case-control studies on <i>VDR</i> rs731236 (Taq1) and risk for MS (NA =  data not available).</p

Gene-gene interaction between the HLA-DRB1*1501 tagging SNP (rs3135388), and the VDR gene polymorphisms in patients with MS.

<p>NPV negative predictive value.</p><p>Combinations for all genotypes were analyzed in 302 MS patients and 309 controls. The frequencies shown correspond to the frequencies of a particular combination of VDR genotype within every rs3135388 (HLADRB1*1501) genotype category.</p

<i>HLADRB1*1501</i> (rs3135388) genotypes and allelic variants in patients with MS, and relation with the evolutive type of MS.

<p>The values in each cell represent: number (percentage; 95% confidence intervals).</p

<i>VDR</i> genotypes and allelic variants in patients with MS, and relation with the evolutive type of MS.

<p>The values in each cell represent: number (percentage; 95% confidence intervals). NPV negative predictive value.</p

<i>Vitamin D3 Receptor</i><b>(</b><i>VDR</i><b>)</b> Gene rs2228570 <b>(</b>Fok1<b>)</b> and rs731236 <b>(</b>Taq1<b>)</b> Variants Are Not Associated with the Risk for Multiple Sclerosis: Results of a New Study and a Meta-Analysis

<div><p>Background</p><p>Some epidemiological, genetic, and experimental data suggest a possible role of vitamin D in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. Data on the possible contribution of several single nucleotide polymorphisms (SNP) in the <i>vitamin D receptor</i> (<i>VDR</i>) gene to the risk for MS are controversial. Several studies suggested an interaction between some SNPs in the <i>VDR</i> gene and <i>HLADRB1*1501</i> in the risk for MS.</p><p>Objectives</p><p>The aim of this study was to investigate a possible influence of the SNPs rs2228570 and rs731236 in the <i>VDR</i> gene in the risk for MS. A secondary objective was to address the possible interactions between <i>VDR</i> genes and <i>HLADRB1*1501</i>.</p><p>Methods</p><p>We analyzed the allelic and genotype frequency of <i>VDR</i> rs2228570, rs731236, and <i>HLADRB1*1501</i> (rs3135388) in 303 patients with MS and 310 healthy controls, using <i>TaqMan</i> Assays. We also conducted a meta-analysis, that was carried out by using the software Meta-Disc 1.1.1 (<a href="http://www.hrc.es/investigacion/metadisc.html" target="_blank">http://www.hrc.es/investigacion/metadisc.html</a>; Unit of Clinical Statistics, Hospital Ramón y Cajal, Madrid, Spain). Heterogeneity between studies in terms of degree of association was tested using the Q-statistic.</p><p>Results</p><p><i>VDR</i> rs2228570 and rs731236 allelic and genotype frequencies did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. <i>HLADRB1*1501</i> showed a high association with the risk of developing MS 4.76(95% C.I.  = 3.14–7.27; p<0.0001). The meta-analysis, after excluding data of one study that was responsible of heterogeneity for rs731236 polymorphism, showed lack of relation of both SNPs with the risk for MS. <i>HLADRB1*1501</i> showed lack of interaction with <i>VDR</i> rs2228570 and rs731236 in increasing MS risk.</p><p>Conclusions</p><p>These results suggest that <i>VDR</i> rs2228570 and rs731236 polymorphisms are not related with the risk for MS, and did not confirm interaction between these <i>VDR</i> SNPs and <i>HLADRB1</i> in the risk for MS.</p></div

Diagnostic odds ratios and 95% confidence intervals (CI) for each study and for pooled samples of (1–a) rs2228570 (Fok1) and (1–b) rs731236 (Taq1).

<p>Diagnostic odds ratios and 95% confidence intervals (CI) for each study and for pooled samples of (1–a) rs2228570 (Fok1) and (1–b) rs731236 (Taq1).</p

<i>HLADRB1*1501</i> (rs3135388) genotype and allelic variants of patients with multiple sclerosis (MS) and healthy volunteers.

<p>The values in each cell represent: number (percentage; 95% confidence intervals CI).</p