title: Association of dopaminergic pathway gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes.
abstract: BACKGROUND
  Genetic markers conferring susceptibility to diabetes specific renal disease remains to be identified for early prediction and development of effective drugs and therapies. Inconsistent results obtained from analysis of genes from classical pathways generate need for examination of unconventional genetic markers having role in regulation of renal function. Experimental and clinical evidences suggest that dopamine is an important natriuretic hormone. Therefore, various genes involved in regulation of dopamine bioavailability could play a role in diabetic chronic renal insufficiency (CRI). We investigated the contribution of 12 polymorphisms from five Dopaminergic pathway genes to CRI among type-2 diabetic Asian Indian subjects.
  
  
  METHODS
  Genetic association of 12 polymorphisms (SNPs) from five genes namely-dopamine receptor-1 (DRD1), DRD2, DRD3, DRD4, andcatechol-O-methyltransferase (COMT) with diabetic CRI was investigated using a case-control approach. Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair wise interactions between SNPs of different genes.
  
  
  RESULTS
  SNPs -141 ins/del C and G>A (1 kb upstream from exon 2) in DRD2 gene showed significant allelic and genotypic association. Allele -141 insC and genotype -141 insC/insC of -141 ins/del C polymorphism, and allele A of G>A SNP were found to be predisposing to CRI. Our result of allelic and genotypic association of -141 insC/delC SNP was also reflected in the haplotypic association. Heterozygous genotype of polymorphism 900 ins/del C in COMT gene was predisposing towards CRI.
  
  
  CONCLUSIONS
  Some polymorphisms in DRD2 and COMT genes are significantly associated with susceptibility to CRI in the Asian Indian population which, if confirmed would be consistent with a suggested role of dopamine metabolism in disease occurrence.
authors: Department of Genetics, University of Delhi South Campus, New Delhi, India. pushplata_prasad114@rediffmail.com
authors: Pushplata
authors: P
authors: Prasad
authors: K M Prasanna
authors: KM
authors: Kumar
authors: A C
authors: AC
authors: Ammini
authors: Arvind
authors: A
authors: Gupta
authors: Rajeev
authors: R
authors: Gupta
authors: B K
authors: BK
authors: Thelma
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011954:Receptors, Dopamine / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000208:ethnology* / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D005819:Genetic Markers; D011954:Receptors, Dopamine; D002394:Catechol O-Methyltransferase