HSPs (heat-shock proteins) are molecular chaperones synthesized under stress conditions, and are involved in renal cell survival and matrix remodelling in acute and chronic renal diseases. In the present study, we investigated whether the HSP70 gene polymorphisms affect susceptibility to DN (diabetic nephropathy) in patients with T2DM (Type 2 diabetes mellitus). The study group consisted of 452 patients with nephropathy. Two control subgroups involved 340 healthy individuals and 132 patients with T2DM lasting ≥10 years who were free of nephropathy. Subjects were genotyped for the HSP70-1 +190 G/C and −110 A/C, HSP70-2 +1267 A/G and HSP70-hom +2437 T/C polymorphisms by PCR, followed by digestion with restriction endonucleases. There were no statistically significant differences in genotype distribution between patients with T2DM with DN and controls for the HSP70-hom polymorphism. Significant differences were observed for HSP70-1 and HSP70-2 polymorphisms. CC homozygotes of the −110 and +190 HSP70-1 polymorphisms were more frequent in patients with T2DM with DN compared with healthy controls (22 compared with 6% and 15 compared with 6.5% respectively; P<0.01). The OR (odds ratio) for the risk allele was 2.17 [95% CI (confidence interval), 1.73–2.72] for the −110 A/C and 1.74 (95% CI, 1.40–2.15) for +190 G/C polymorphisms. A strong association with DN was found for the +1267 HSP70-2 polymorphism. The GG genotype and the G allele were associated with DN, with the OR for the G allele being 4.77 (95% CI, 3.81–5.96). All GG homozygotes in the patient group had higher LDL (low-density lipoprotein)-cholesterol levels than AA homozygotes (P<0.01), suggesting that the observed effect might be associated with this cardiovascular risk factor. These patients progressed faster to end-stage renal failure than those with other genotypes. In conclusion, our results indicate that the HSP70-1 and HSP70-2 polymorphisms are associated with renal complications in T2DM and may be useful in identifying patients with increased risk of DN.
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Research Article|
November 28 2008
Heat-shock protein gene polymorphisms and the risk of nephropathy in patients with Type 2 diabetes
Monika Buraczynska;
1Laboratory for DNA Analysis and Molecular Diagnostics, Department of Nephrology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland
Correspondence: Professor Monika Buraczynska (email [email protected]).
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Andrzej Swatowski;
Andrzej Swatowski
1Laboratory for DNA Analysis and Molecular Diagnostics, Department of Nephrology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland
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Kinga Buraczynska;
Kinga Buraczynska
1Laboratory for DNA Analysis and Molecular Diagnostics, Department of Nephrology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland
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Michal Dragan;
Michal Dragan
1Laboratory for DNA Analysis and Molecular Diagnostics, Department of Nephrology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland
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Andrzej Ksiazek
Andrzej Ksiazek
1Laboratory for DNA Analysis and Molecular Diagnostics, Department of Nephrology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland
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Publisher: Portland Press Ltd
Received:
November 20 2007
Revision Received:
March 19 2008
Accepted:
May 30 2008
Accepted Manuscript online:
May 30 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2009 Biochemical Society
2009
Clin Sci (Lond) (2009) 116 (1): 81–86.
Article history
Received:
November 20 2007
Revision Received:
March 19 2008
Accepted:
May 30 2008
Accepted Manuscript online:
May 30 2008
Citation
Monika Buraczynska, Andrzej Swatowski, Kinga Buraczynska, Michal Dragan, Andrzej Ksiazek; Heat-shock protein gene polymorphisms and the risk of nephropathy in patients with Type 2 diabetes. Clin Sci (Lond) 1 January 2009; 116 (1): 81–86. doi: https://doi.org/10.1042/CS20070411
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