72, P = 0.08), and EPHX*3 HH versus YY among solvent exposed had the lowest OR (0.30, P = 0.14). A logistic regression analysis for the different polymorphisms, sex, age, and exposures did not

show any confounding effects except that increasing age and male sex increased the risk of Selleckchem Daporinad cryptogenic polyneuropathy. Interactions between genes were analyzed and confirmed the increased OR for GSTT1, which was strongest if the patients had the HH form of EPHX*3 (OR 2.37). Table 3 Effects of genetic polymorphisms Inhibitors,research,lifescience,medical in different exposures (exposed cases and controls) Discussion In this epidemiological case–control study of patients with cryptogenic polyneuropathy, we examined the association of GSTM1 and GSTT1 null polymorphisms and EPHX1 exon 3 HH polymorphism

in relation to several environmental and chemical exposures. Although we did not Inhibitors,research,lifescience,medical find any statistically significant increased risk, the GSTT1 null genotype was associated with an almost twofold increased risk of polyneuropathy. Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired Inhibitors,research,lifescience,medical metabolism of toxic substances and reactive oxygen that could lead to nerve damage, involving multiple sites along motor and sensory axons in the peripheral nervous system. This may result in axonal atrophy or axonal swelling, leading to progressive distal axonal degeneration. The myelin sheath may break down concomitantly with the axon. This could Inhibitors,research,lifescience,medical contribute to, or directly result in, an axonal or combined axonal-demyelinating neuropathy. Components of cigarette smoke

are examples of exogenous substrates that are toxic and, furthermore, are subject to bioactivation and may both directly and indirectly be neurotoxic. We found a nearly fourfold Inhibitors,research,lifescience,medical increased risk of polyneuropathy in GSTT1 null smokers that almost achieved statistical significance. Teunissen and co-authors reported an OR of 2.1 for current smoking in patients with chronic idiopathic axonal polyneuropathy (Teunissen et al. 2002), and it has also been found that tobacco use may predispose to earlier development and more severe symptoms of diabetic neuropathy (Tesfaye et al. 2005). Our data indicate that this risk might be explained by smokers second carrying certain genetic polymorphisms leading to impaired detoxification of the toxic compounds in cigarette smoke. In a study of solvent-induced chronic toxic encephalopathy, an increased risk ratio of 2.5 for the GSTM1 null genotype was found in smokers and a risk ratio of 1.5 for the GSTT1 null genotype in the overall population. In nonsmokers, the GSTM1 null genotype did not confer any risk for chronic toxic encephalopathy. None of the studied mEPHX polymorphisms were associated with an increased risk. The mechanism for the toxicity of cigarette smoke on nerves is not known, but it has been speculated that it is mediated by chemicals in the smoke where PAHs are regarded as the most important component.