title: Association Analysis of Polymorphisms in Genes Related to Oxidative Stress in South Indian Type 2 Diabetic Patients with Retinopathy.
abstract: BACKGROUND
  Diabetic Retinopathy (DR) is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and is polygenic with a multitude of genes contributing to disease susceptibility. The present study aimed at exploring the association between DR and seven polymorphisms in oxidative stress-related genes, i.e. ACE, eNOS, p22phox subunit of NAD(P)H oxidase, PARP-1 and XRCC1 in South Indian T2DM subjects.
  
  
  METHODS
  The study included 149 T2DM subjects with DR (diagnosed through funduscopic examination) and 162 T2DM patients with no evidence of DR. The selected polymorphisms were genotyped by polymerase chain reaction (PCR) and Taqman allele discrimination assay.
  
  
  RESULTS
  There was no significant difference in the genotype and allele distribution of ACE ins/del, eNOS-786T>C, 894G>T, 4a4b and p22phox 242C>T polymorphisms between T2DM groups with and without DR. Contrastingly, there appeared to be a significant association of PARP-1 Val762Ala and XRCC1 Arg399Gln polymorphisms with DR, wherein 762Ala allele seemed to confer significant protection against DR (p = 0.01; OR = 0.51 [0.3-0.86]), while the presence of 399Gln allele was associated with an enhanced risk for DR (p = 0.02; OR = 1.52 [1.07-2.15]). Multiple logistic regression analysis revealed a significant and independent association of Val762Ala and Arg399Gln polymorphisms and other putative risk factors with DR in T2DM individuals.
  
  
  CONCLUSIONS
  The polymorphisms in the DNA repair genes PARP-1 and XRCC1 tended to associate significantly with DR. While Val762Ala polymorphism was associated with reduced susceptibility to DR, the Arg399Gln polymorphism contributed an elevated to risk for DR in South-Indian T2DM individuals.
authors.affiliation: a Department of Genetics , Osmania University , Hyderabad , India and.
authors.forename: Parimala
authors.initials: P
authors.lastname: Narne
authors.affiliation: a Department of Genetics , Osmania University , Hyderabad , India and.
authors.forename: Kamakshi Chaithri
authors.initials: KC
authors.lastname: Ponnaluri
authors.affiliation: b Department of Medicine , Deccan College of Medical Sciences , Hyderabad , India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Siraj
authors.affiliation: a Department of Genetics , Osmania University , Hyderabad , India and.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ishaq
mesh_terms: D044466:Asian People; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C086986:CYBA protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D045643:DNA Repair Enzymes
keywords: Diabetic retinopathy; oxidative stress; polymorphism; type 2 diabetes mellitus