Heat-shock protein gene polymorphisms and the risk of nephropathy in type 2 diabetes patients

Monika Buraczynska (1) , Andrzej Swatowski , Kinga Buraczynska , Michal Dragan , Andrzej Ksiazek

1 Nephrology

Heat-shock proteins (HSPs) are molecular chaperones synthesized under stress conditions. HSPs are involved in renal cell survival and matrix remodeling in acute and chronic renal diseases. We investigated whether the HSP70 gene polymorphisms affect susceptibility to nephropathy in type 2 diabetes patients.The study group consisted of 240 patients with nephropathy. Two control subgroups involved: 275 healthy individuals and 132 patients with type 2 diabetes lasting ≥ 10 years, 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 polymerase chain reaction (PCR) followed by digestion with restriction endonucleases. There were no statistically significant differences in genotype distribution between diabetic nephropathy (DN) patients and controls for the HSP70-hom polymorphism. Significant differences were observed for HSP70-1 and HSP70-2 polymorphisms. The CC homozygotes of the -110 and +190 HSP70-1 polymorphisms were more frequent in DN patients than in healthy controls (22 vs. 6 % and 15 vs. 7 %,respectively, p<0.01). The OR for the risk allele was 2.17 (95 % CI 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 OR for the G allele 4.77 (95 % CI 3.81-5.96). All GG homozygotes in patient group had higher LDL cholesterol level than AA homozygotes (p<0.01), suggesting that the observed effect might be associated with cardiovascular risk factor. These patients progressed faster to end-stage renal failure than those with other genotypes. Our results indicate that the HSP70-1 and HSP70-2 polymorphisms are associated with renal complications in type 2 diabetes and may be useful in identifying patients with increased risk of diabetic nephropathy.

Mots clés: Medicine

Monika Buraczynska, Andrzej Swatowski, Kinga Buraczynska, Michal Dragan, Andrzej Ksiazek. Heat-shock protein gene polymorphisms and the risk of nephropathy in type 2 diabetes patients. Clinical Science, 2008, 116 (1), pp.81-86. ⟨10.1042/CS20070411⟩. ⟨hal-00479416⟩