(Journal Article): Manganese Superoxide Dismutase Alanine to Valine Polymorphism and Risk of Neuropathy and Nephropathy in Egyptian Type 1 Diabetic Patients
 
El Masry TM, Abou Zahra MA, El Tawil MM, Khalifa RA (Department of Clinical Pathology, Ain Shams University Hospital, Cairo, Egypt, tarek_msry(at)yahoo.com )
 
IN: Rev Diabetic Stud 2005; 2(2):70-74
Impact Factor(s) of Rev Diabetic Stud: 0.125 (2006)

Fulltext:    HTML  PDF

ABSTRACT: Oxidative stress, characterized by a marked increase in the level of oxygen free radicals (OFR), has been implicated in the development of diabetic microangiopathic complications, such as diabetic neuropathy (DN) and nephropathy (DP). Antioxidant enzymes may protect against the rapid onset and progression of microangiopathy, by reducing the excess of OFR and peroxides. Mutations and polymorphisms in genes encoding such enzymes may therefore result in a predisposition to this disorder. AIM: we investigated the role of genes encoding the antioxidant enzyme, mitochondrial superoxide dismutase (Mn-SOD2), in DN and DP pathogenesis in an Egyptian population. We studied Ala(-9)Val polymorphism of the Mn-SOD2 gene in type 1 diabetic patients (n = 65) with DN (n = 40) or DP (n = 45). METHODS: we used polymerase chain reaction (PCR) assays with restriction fragment length polymorphism for rapid detection of polymorphisms. These assays involved the use of mismatch PCR primers to create restriction sites in the amplified product only in presence of the polymorphic base. The PCR product was then digested with AgeI restriction enzyme to detect Ala(-9)Val polymorphic sites. RESULTS: the frequencies of the Ala allele (odds ratio (OR) = 0.438, 95% CI of 0.247 - 0.778) and the Ala/Ala genotype (OR = 0.26, 95% CI of 1.39 - 10.266) were significantly lower in diabetic neuropathy patients. In contrast, the frequencies of the Val allele (OR = 2.282, 95% CI of 1.286 - 4.05) and the homozygous Val/Val genotype (OR = 6.68, 95% CI of 0.3 - 0.76) were significantly higher in patients with DN than diabetics without neuropathy. Although the Val allele was more frequently detected in DP patients than diabetics without nephropathy (OR = 3.2), this difference was statistically non-significant. In conclusion, Ala(-9)Val substitution in the Mn-SOD2 gene was associated with DN in Egyptian diabetic children but not a significant factor in diabetic patients with nephropathy.

TYPE OF PUBLICATION: Original article

REFERENCES:

1. Svensson M, Eriksson JW, Dahlquist G. Early glycemic control, age at onset, and development of microvascular com-plications in childhood-onset type 1 diabetes: a population-based study in northern Sweden. Diabetes Care 2004. 27:955-962. [DOD]
2. Rosenblum JS, Gilula NB, Lerner RA. On signal sequence polymorphisms and diseases of distribution. Proc Natl Acad Sci U S A 1996. 93:4471-4473. [DOD]
3. Hori H, Ohmori O, Shinkai T, Kojima H, Okano C, Su-zuki T, Nakamura J. Manganese superoxide dismutase gene polymorphism and schizophrenia: relation to tardive dyskine-sia. Neuropsychopharmacology 2000. 23:170-177. [DOD]
4. Budowle B, Chakraborty R, Giusti AM, Eisenberg AJ, Al-len RC. Analysis of the VNTR locus D1S80 by the PCR fol-lowed by high-resolution PAGE. Am J Hum Genet 1991. 48:137-144. [DOD]
5. Roff DA, Bentzen P. The statistical analysis of mitochondrial DNA polymorphisms: chi 2 and the problem of small samples. Mol Biol Evol 1989. 6:539-545. [DOD]
6. Chistyakov DA, Savost’anov KV, Zotova EV, Nosikov VV. Polymorphisms in the Mn-SOD and EC-SOD genes and their relationship to diabetic neuropathy in type 1 diabetes mellitus. BMC Med Genet 2001. 2:4. [DOD]
7. Grasbon-Frodl EM, Kosel S, Riess O, Muller U, Mehraein P, Graeber MB. Analysis of mitochondrial targeting sequence and coding region polymorphisms of the manganese superox-ide dismutase gene in German Parkinson disease patients. Bio-chem Biophys Res Commun 1999. 255:749-752. [DOD]
8. Strokov IA, Bursa TR, Drepa OI, Zotova EV, Nosikov VV, Ametov AS. Predisposing genetic factors for diabetic polyneuropathy in patients with type 1 diabetes: a population-based case-control study. Acta Diabetol 2003. 40Suppl2:S375-379. [DOD]
9. Nosikov VV. Genomics of type I diabetes mellitus and its late complications. Mol Biol (Mosk) 2004. 38:150-164. [DOD]
10. Nomiyama T, Tanaka Y, Piao L, Nagasaka K, Sakai K, Ogihara T, Nakajima K, Watada H, Kawamori R. The polymorphism of manganese superoxide dismutase is associ-ated with diabetic nephropathy in Japanese type 2 diabetic pa-tients. J Hum Genet 2003. 48:138-141. [DOD]
11. Akyol O, Yanik M, Elyas H, Namli M, Canatan H, Akin H, Yuce H, Yilmaz HR, Tutkun H, Sogut S, Herken H, Ozyurt H, Savas HA, Zoroglu SS. Association between Ala-9Val polymorphism of Mn-SOD gene and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2005. 29:123-131. [DOD]