12 research outputs found
Renalase Gene Polymorphisms in Patients With Type 2 Diabetes, Hypertension and Stroke
Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent amine oxidase. It is secreted by the kidney and metabolizes circulating catecholamines. Renalase has significant hemodynamic effects, therefore it is likely to participate in the regulation of cardiovascular function.The aim of our study was to investigate the involvement of renalase gene polymorphisms in hypertension in type 2 diabetes patients. A total of 892 patients and 400 controls were genotyped with three SNPs in the renalase gene. The C allele of rs2296545 SNP was associated with hypertension (P < 0.01). For rs2576178 SNP, frequencies in hypertensive patients differed from controls, but not from normotensive patients. For rs10887800 SNP, the differences in the G allele frequencies were observed in hypertensive patients with stroke, with 66% of patients being GG homozygotes. To confirm observed association we later genotyped 130 stroke patients without diabetes. The OR for risk allele was 1.79 (95% CI 1.33–2.41). In conclusion, the renalase gene polymorphism was associated with hypertension in type 2 diabetes patients. The most interesting result is a strong association of the rs10887800 polymorphism with stroke in patients with and without diabetes. The G allele of this polymorphism might thus be useful in identifying diabetes patients at increased risk of stroke
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference