The 262T>C promoter polymorphism of the catalase gene is associated with diabetic neuropathy in type 1 diabetic Russian patients.
OBJECTIVE
Oxidative stress plays an important role in the development of diabetic neuropathy (DN). Antioxidant enzymes reduce enhanced oxidative stress in the peripheral nerve. Genetic variations within the antioxidant genes therefore could be implicated in the pathogenesis of DN.


METHODS
Using a PCR-RFLP assay, a total of 216 Russian type 1 diabetic (T1D) patients with DN and 250 T1D individuals without DN have been tested to verify whether the -262T > C and 1167C > T polymorphisms of the catalase (CAT), 197Pro > Leu amino acid substitution of the glutathione peroxidase 1 (GPX1) and +/null polymorphism of the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes contribute to susceptibility to DN.


RESULTS
Association between the -262T > C polymorphism of the CAT gene and DN was shown. The -262TT genotype of the CAT gene was significantly associated with higher erythrocyte catalase activity in blood of DN patients compared to the -262CC genotype (17.8 +/- 2.7 x 104 IU/g Hb vs. 13.5 +/- 3.2 x 104 IU/g Hb, P = 0.0022).


CONCLUSIONS
These data suggest a protective role of the -262T allele of the CAT gene against the rapid development of DN in T1D (Odds Ratio = 0.7 [95% confidence interval 0.54-0.9], P = 0.002).
Chistiakov
D A
DA
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267-0529, USA. dimitry.chistiakov@uc.ecu
Zotova
E V
EV
Savost'anov
K V
KV
Bursa
T R
TR
Galeev
I V
IV
Strokov
I A
IA
Nosikov
V V
VV
D000328:Adult; D002374:Catalase / Q000235:genetics*; D003596:Cytosine; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics*; D003929:Diabetic Neuropathies / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012426:Russia; D013941:Thymine
D003596:Cytosine; D004247:DNA; D002374:Catalase; D013941:Thymine