Search

Background/Aims: Several single nucleotide polymorphisms (SNPs) in the PITX3 gene have been associated with the risk for Parkinson's disease (PD). We conducted a systematic review and a meta-analysis including all the studies published on the risk of PD related with these polymorphisms. Methods: The systematic review was done using several databases. Eligible studies were included in the meta-analysis that was carried out using Meta-DiSc 1.1.1 software. Heterogeneity between studies was tested using the Q-statistic. Results: The meta-analysis included eight association studies for the PITX3 rs3758549 SNP (4,052 PD patients, 3,949 controls), eight studies for the PITX3 rs2281983 SNP (4,309 PD patients, 4,287 controls), and six studies for the rs4919621 SNP (2,724 PD patients, 2,285 controls), and the risk for PD, global diagnostic odds ratios (95% confidence intervals) for rs3758549, rs2281983, and rs4919621 were, respectively, 1.00 (0.89-1.12) (p = 0.979), 0.99 (0.91-1.09) (p = 0.896), and 0.98 (0.83-1.16) (p = 0.844) for the total group. The separate analysis in Caucasian and Chinese subjects on the frequency of the minor allele of the three SNPs analyzed did not show significant differences between PD patients and controls in both subgroups. rs2281983 and rs4919621 SNPs were related with early-onset PD risk in Caucasians. Conclusion: The results of the meta-analysis suggest that rs3758549, rs2281983, and rs4919621 SNPs are not major determinants of the risk for PD. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Many patients with essential tremor (ET) develop acute adverse effects to primidone. We investigated the association between CYP2C19 polymorphism (possibly related to primidone metabolism) and the risk for developing essential ET and acute adverse effects to primidone. Leukocytary DNA from 200 ET patients and 300 healthy controls was studied for the genotype CYP2C19 and the occurrence of CYP2C19 allelic variants by using allele-specific PCR amplification and Sma I and BamH I RFLP analyses. The frequencies of the genotype CYP2C19*1/CYP2C19*2 and of the allelic variant CYP2C19*2 were significantly higher in ET patients than in controls. The mean age at onset of ET did not differ significantly between patients with genotypes CYP2C19*1/CYP2C19*2andCYP2C19*1/CYP2C19*1. The frequencies of the genotype CYP2C19*1/CYP2C19*2 and the allelic variant CYP2C19*2 were similar in ET patients who developed acute adverse effects to primidone, in those who tolerated primidone and in controls; the frequencies were also similar in patients with head, voice, tongue and chin tremor compared with controls. These results suggest that heterozygosis CYP2C19*1/CYP2C19*2 is associated with the risk for ET, but not with the age at onset of ET, the presentation of acute side effects of primidone, or the existence of head, voice, tongue or chin tremor. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The cytochrome P[sub 450] CYP2D6 is a polymorphic drug-metabolizing enzyme that is involved in the metabolism of several drugs and xenobiotics. Several independent studies indicate that the CYP2D6 metabolic status is a secondary factor in the risk of developing lung cancer, with individuals with high activity being at increased risk. The occurrence of functionally active duplications of the CYP2D6 gene is a phenomenon that affects 3–8% of Caucasians and up to 30% in some ethnic groups. These duplications cause ultrarapid metabolism of CYP2D6 substrates. In order to establish whether the highest CYP2D6 enzyme activity is associated with an increased risk of cancer, we analyzed the frequency of CYP2D6 gene duplications and enzyme-inactivating mutations in 199 Caucasian patients with lung or larynx cancer and in 335 healthy controls. A significantly increased frequency of carriers of the CYP2D6 gene duplication were found among lung and larynx cancer patients (13%), as compared with healthy controls (6.9%; p < 0.02). The frequency of the mutated active CYP2D6*9 allele was increased in lung cancer patients (p < 0.01) but not in larynx cancer patients. Global findings indicate that over 20% patients with lung or larynx cancer show CYP2D6 genotypes leading to ultrarapid metabolism or to the expression of an enzyme with altered kinetics (p < 0.01 vs. healthy controls). This may influence the metabolism of CYP2D6 substrates, including antineoplastic drugs and opioid derivatives used for pain relief in cancer patients. These patients would require higher doses than those considered as standard. We conclude that dosages for CYP2D6 substrates should be adapted to lung and larynx cancer patients.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]