Dataset Information

Further evidence for the association of CYP2D6*4 gene polymorphism with Parkinson's disease: a case control study.

ABSTRACT: BACKGROUND:Genetic and environmental risk factors play an important role for the susceptibility to sporadic Parkinson's disease (PD). It was hypothesized that a splice variant of the CYP2D6 gene (CYP2D6*4 allele) is associated with PD because it alters the ability to metabolize toxins and in particular neurotoxins. CYP2D6 codes for the drug metabolizing enzyme debrisoquine 4-hydroxylase. The CYP2D6*4 variant results in an undetectable enzyme activity and consequently in a reduction in metabolism of some toxins. METHODS:Some of agricultural chemicals have neurotoxic potential and CYP2D6 is involved in their detoxification. Thus, we conducted a case control study to investigate the association of the CYP2D6*4 with PD in a Pakistani subpopulation that is known to be exposed to high levels of some agricultural pesticides, insecticides and herbicides. RESULTS:We found a significantly higher allele and genotype frequency of the CYP2D6*4 variant in 174 sporadic PD patients when compared to 200 controls. In addition, there was a trend to an earlier age of PD onset and a tremor dominant phenotype in CYP2D6*4 variant carriers. CONCLUSION:Our data provide further evidence that a poor metabolizer status may increase the risk to develop PD especially in populations that are exposed to environmental toxins.

SUBMITTER: Anwarullah

PROVIDER: S-EPMC5493842 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Further evidence for the association of CYP2D6*4 gene polymorphism with Parkinson's disease: a case control study.

Anwarullah Aslam Muhammad M Badshah Mazhar M Abbasi Rashda R Sultan Aneesa A Khan Kafaitullah K Ahmad Nafees N von Engelhardt Jakob J

Genes and environment : the official journal of the Japanese Environmental Mutagen Society 20170701

<h4>Background</h4>Genetic and environmental risk factors play an important role for the susceptibility to sporadic Parkinson's disease (PD). It was hypothesized that a splice variant of the <i>CYP2D6</i> gene (<i>CYP2D6*4</i> allele) is associated with PD because it alters the ability to metabolize toxins and in particular neurotoxins. <i>CYP2D6</i> codes for the drug metabolizing enzyme debrisoquine 4-hydroxylase. The CYP2D6*4 variant results in an undetectable enzyme activity and consequently ...[more]

PMID: 28680508

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Project description:OBJECTIVE:Several published studies have investigated the association between the -308G/A (rs1800629) polymorphism in the tumor necrosis factor-? (TNF-?) gene and the risk of dilated cardiomyopathy (DCM). However, the TNF-? gene polymorphism has a controversial role in the pathogenesis of DCM among different populations. In the present study, a meta-analysis was performed to resolve this inconsistency. METHODS:Potentially eligible papers reporting an association between the TNF-? rs1800629 polymorphism and DCM susceptibility were searched in 4 databases including PubMed, EMBASE, Chinese Biomedical Database (CBM), and the Cochrane Library up to April 1, 2018. The odds ratio (OR) with its 95% confidence interval (CI) was used to estimate the strength of the associations. Subgroup analysis based on the ethnicity, studies with or without ischemic and valvular DCM was conducted. Publication bias detection was conducted using Begg test. RESULTS:Nine papers detailing case-control studies were included, reporting a total of 1339 DCM cases and 1677 healthy controls. The meta-analysis results indicated that TNF-? rs1800629 was associated with increased DCM susceptibility in the populations studied under the heterozygous model (AG vs GG: OR?=?1.91, 95% CI?=?1.05-3.50, P?=?.035) and dominant model (AG?+?AA vs GG: OR?=?1.87, 95% CI?=?1.01-3.45, P?=?.046). In the subgroup analysis for ethnicity, rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians under the 5 models (A vs G: OR?=?2.87, 95% CI?=?1.56-5.30, P?=?.001; AA vs GG: OR?=?3.95, 95% CI?=?1.13-13.82, P?=?0.031; AG vs GG: OR?=?3.8, 95% CI?=?1.57-9.19, P?=?.003; AA vs GG?+?AG: OR?=?2.51, 95% CI?=?1.41-4.49, P?=?.002; AG?+?AA vs GG: OR?=?3.77, 95% CI?=?1.54-9.20, P?=?.004). CONCLUSION:There may be a moderate association between TNF-? rs1800629 polymorphism and DCM susceptibility in the whole populations studied; however, TNF-? rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians, which indicates that such associations may be different between ethnicities.

Dataset Information

Further evidence for the association of CYP2D6*4 gene polymorphism with Parkinson's disease: a case control study.

Publications

Further evidence for the association of CYP2D6*4 gene polymorphism with Parkinson's disease: a case control study.

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