%0 Journal Article
	%A Ireneusz Majsterek and  Anna Merecz and  Agnieszka Sliwinska and  Marcin Kosmalski and  Jacek Kasznicki and 
Jozef Drzewoski
	%D 2012
	%J International Journal of Medical and Health Sciences
	%B World Academy of Science, Engineering and Technology
	%I Open Science Index 70, 2012
	%T Role of Oxidative DNA Damage in Pathogenesis of Diabetic Neuropathy
	%U https://publications.waset.org/pdf/10153
	%V 70
	%X Oxidative stress is considered to be the cause for onset
and the progression of type 2 diabetes mellitus (T2DM) and
complications including neuropathy. It is a deleterious process that
can be an important mediator of damage to cell structures: protein,
lipids and DNA. Data suggest that in patients with diabetes and
diabetic neuropathy DNA repair is impaired, which prevents effective
removal of lesions. Objective: The aim of our study was to evaluate
the association of the hOGG1 (326 Ser/Cys) and XRCC1 (194
Arg/Trp, 399 Arg/Gln) gene polymorphisms whose protein is
involved in the BER pathway with DNA repair efficiency in patients
with diabetes type 2 and diabetic neuropathy compared to the healthy
subjects. Genotypes were determined by PCR-RFLP analysis in 385
subjects, including 117 with type 2 diabetes, 56 with diabetic
neuropathy and 212 with normal glucose metabolism. The
polymorphisms studied include codon 326 of hOGG1 and 194, 399
of XRCC1 in the base excision repair (BER) genes. Comet assay was
carried out using peripheral blood lymphocytes from the patients and
controls. This test enabled the evaluation of DNA damage in cells
exposed to hydrogen peroxide alone and in the combination with the
endonuclease III (Nth). The results of the analysis of polymorphism
were statistically examination by calculating the odds ratio (OR) and
their 95% confidence intervals (95% CI) using the ยครง2-tests. Our data
indicate that patients with diabetes mellitus type 2 (including those
with neuropathy) had higher frequencies of the XRCC1 399Arg/Gln
polymorphism in homozygote (GG) (OR: 1.85 [95% CI: 1.07-3.22],
P=0.3) and also increased frequency of 399Gln (G) allele (OR: 1.38
[95% CI: 1.03-1.83], P=0.3). No relation to other polymorphisms
with increased risk of diabetes or diabetic neuropathy. In T2DM
patients complicated by neuropathy, there was less efficient repair of
oxidative DNA damage induced by hydrogen peroxide in both the
presence and absence of the Nth enzyme. The results of our study
suggest that the XRCC1 399 Arg/Gln polymorphism is a significant
risk factor of T2DM in Polish population. Obtained data suggest a
decreased efficiency of DNA repair in cells from patients with
diabetes and neuropathy may be associated with oxidative stress.
Additionally, patients with neuropathy are characterized by even
greater sensitivity to oxidative damage than patients with diabetes,
which suggests participation of free radicals in the pathogenesis of
neuropathy.
	%P 494 - 501