Leu54Phe and Val762Ala polymorphisms in the poly(ADP-ribose)polymerase-1 gene are associated with diabetic polyneuropathy in Russian type 1 diabetic patients.
Poly(ADP-ribose) polymerase-1 (PARP-1) is an ubiquitous DNA-binding protein involved in the cellular response to various genotoxic agents. Excessive PARP-1 activation is known to lead to the depletion of intracellular NAD+ and ATP pools and hence to threat cell survival. Therefore, PARP-1 could be involved in neuronal death and contribute to the development of diabetic polyneuropathy (DPN). This study addressed the association of Leu54Phe and Val762Ala polymorphisms of PARP-1 with DPN in Russian type 1 diabetic (T1D) patients. Eighty-six T1D patients with severe DPN and 93 T1D patients with no clinical signs of DPN have been studied by a polymerase chain reaction restriction fragment length polymorphism approach. Using Fisher's exact test revealed the association of the Phe54 and Val762 variants of PARP-1 (odds ratio (OR), 1.66 and 2.88, respectively) with increased risk of DPN in T1D. These results suggest that the PARP1 gene is involved in the pathogenesis of diabetic neuropathy in a Russian population. Additionally, a logistic regression analysis revealed a significant association between the neurological variances such as vibration detection threshold (OR, 2.08), vibration and temperature perception thresholds (OR, 1.32 and 1.67, respectively), and sensory and motor nerve conduction velocities (OR, 2.34 and 2.58, respectively), with DPN.
National Research Center GosNIIgenetika, Moscow, Russia.
Alexey G
AG
Nikitin
Dariya A
DA
Chudakova
Igor A
IA
Strokov
Tamara R
TR
Bursa
Dimitry A
DA
Chistiakov
Valery V
VV
Nosikov
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D000704:Analysis of Variance; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000208:ethnology; D003929:Diabetic Neuropathies / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012426:Russia; D044465:White People
D011065:Poly(ADP-ribose) Polymerases