S Visvikis — Page 6 | PubMed Health

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[Glutathione S-transferases genetic polymorphisms and human diseases: overview of epidemiological studies].

Glutathione S-transferases (GST), xenobiotic-metabolising enzymes, are involved in the metabolic detoxification of various environmental carcinogens. Particular genetic polymorphisms of these enzymes have been shown to influence individual susceptibility against various pathologies including cancer, cardiovascular and respiratory diseases. The results from the meta-analysis indicate that GSTM1*0 null allele was associated with enhanced risk for lung (OR (95% IC) = 1,17 (1,07-1,27)), bladder (OR = 1,44 (1,23-1,68) and larynx cancer (OR = 1,42 (1,10-1,84)). GSTT1 null genotype was associated with increased astrocytomas (OR = 2,36 (1,41-3,94)) and meningiomas (OR = 3,57 (1,82-6,92)) cancer risk. GSTP1 allelic polymorphism influence the development of bladder cancer in smokers (OR = 2,40 (1,12-4,95)) and occupational asthma (OR = 3,5 (2,7-4,6)). Finally, GSTM1*0 null allele and GSTT1*1 functional allele were associated with increased risk for coronary heart diseases in smokers (OR = 2,30 (1,40-9,00)) and OR = 2,5 (1,30-4,80), respectively). The GSTT1*1 functional allele was also significantly associated with increased risk of lower extremity arterial disease (OR = 3,60 (1,40-9,00). These epidemiological data suggest that genetic GST polymorphisms influence the individual susceptibility to these diseases. Contrary to cardiovascular disease, no evidence of interaction between GST genotype and smoking status was found in lung cancer but it has not been studied in other cancers. Consequently, other works are necessary to study the potential interaction between GST genotype and environmental carcinogens including tobacco smoke extract.

Cardiovascular Diseases↗

PubMedDate not supplied

[Alzheimer disease: hypotheses implicating apolipoproteins E].

The most promising discovery in the study of Alzheimer's disease (AD) markers is undoubtedly the implication of apolipoprotein E (apoE). The gene of this apoliprotein is located on chromosome 19 and is characterized by three common alleles epsilon 2, epsilon 3 and epsilon 4 giving raise to 6 genotypes and 6 protein phenotypes. ApoE is well known for its role in cholesterol transport. Different studies have been performed, giving major arguments in favor of an important role of apoE in the pathophysiology of AD. These include the discovery of the relationship between the epsilon 4 allele and AD, the ability of this protein to form complexes with beta amyloid protein (A beta) in seniles plates, its presence in neurofibrillary tangles and in vessels of AD patients. Another important finding is the differential interaction between the different isoforms of apoE and tau protein. Some of the hypotheses implicate the role of different apoE isoforms on the growth and extension of neurones, perhaps by a receptor mediated pathway. It has been suggested that apoE acts as a pathological chaperone protein, or alternatively that it protects neurons by regulation of the cell membrane and modifying calcium homeostasis. It is clear that apoE genotype determination alone cannot be used for diagnosis of AD. The presence of epsilon 4 allele is only one of several risk factors for the development of the disease. Other factors may also be implicated and are the subject of ongoing research.

Alzheimer Disease↗