title: Uncoupling protein 2 and 3 gene polymorphisms and their association with type 2 diabetes in asian indians.
abstract: BACKGROUND
  this study examined the association of -866G/A, Ala55Val, 45bpI/D, and -55C/T polymorphisms at the uncoupling protein (UCP) 3-2 loci with type 2 diabetes in Asian Indians.
  
  
  METHODS
  a case-control study was performed among 1,406 unrelated subjects (487 with type 2 diabetes and 919 normal glucose-tolerant [NGT]), chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in Southern India. The polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Haplotype frequencies were estimated using an expectation-maximization algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies.
  
  
  RESULTS
  the genotype (P = 0.00006) and the allele (P = 0.00007) frequencies of Ala55Val of the UCP2 gene showed a significant protective effect against the development of type 2 diabetes. The odds ratios (adjusted for age, sex, and body mass index) for diabetes for individuals carrying Ala/Val was 0.72, and that for individuals carrying Val/Val was 0.37. Homeostasis insulin resistance model assessment and 2-h plasma glucose were significantly lower among Val-allele carriers compared to the Ala/Ala genotype within the NGT group. The genotype (P = 0.02) and the allele (P = 0.002) frequencies of -55C/T of the UCP3 gene showed a significant protective effect against the development of diabetes. The odds ratio for diabetes for individuals carrying CT was 0.79, and that for individuals carrying TT was 0.61. The haplotype analyses further confirmed the association of Ala55Val with diabetes, where the haplotypes carrying the Ala allele were significantly higher in the cases compared to controls.
  
  
  CONCLUSIONS
  Ala55Val and -55C/T polymorphisms at the UCP3-2 loci are associated with a significantly reduced risk of developing type 2 diabetes in Asian Indians.
authors.affiliation: Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, Chennai, India.
authors.forename: Karani S
authors.initials: KS
authors.lastname: Vimaleswaran
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Radha
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: Partha P
authors.initials: PP
authors.lastname: Majumder
authors.forename: Manchanahalli R
authors.initials: MR
authors.lastname: Sathyanarayana Rao
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D004247:DNA; D006442:Glycated Hemoglobin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human