Interaction between the UCP2-866G/A, mtDNA 10398G/A and PGC1alpha p.Thr394Thr and p.Gly482Ser polymorphisms in type 2 diabetes susceptibility in North Indian population

Hum Genet. 2007 Dec;122(5):535-40. doi: 10.1007/s00439-007-0421-4. Epub 2007 Aug 14.


In the recent past, we have observed a possible role of 10398A and 16189C mtDNA and PGC1alpha p.Thr394Thr (rs2970847) and p.Gly482Ser (rs8192673) variant genotypes providing susceptibility/protection against type 2 diabetes mellitus (T2DM) in two North Indian population groups. These initial observations encouraged us to look at the candidate genes in combination with -866G/A (rs659366) polymorphism in uncoupling protein 2 (UCP2) in a single study of a relatively large sample size, constituted of both the cohorts, to unravel an interesting outcome of an additive interaction in-between the studied genes. In a total of 1,686 individuals (762 cases and 924 controls) belonging to Indo-European linguistic group from North India, a comparison of risk genotype combinations of: UCP2-866GG, mtDNA 10398A and PGC1alpha p.Thr394Thr or p.Gly482Ser against the protective genotypes: UCP2-866XA, mtDNA 10398G and PGC1alpha p.Thr394Thr (nominal P value = 1.75 x 10(-14), Odds ratio, OR = 5.29, 3.40-8.22 at 95% CI) or PGC1alpha p.Gly482Ser (nominal p value = 4.42 x 10(-24), OR = 8.59, 5.53-13.35 at 95% CI), showed a highly significant difference and increased ORs. In a complex disease, it is always encouraging to find an additive interaction of multiple small effects of the studied candidate gene variations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Amino Acid Substitution
  • Case-Control Studies
  • DNA, Mitochondrial / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Heat-Shock Proteins / genetics*
  • Humans
  • India
  • Ion Channels / genetics*
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Odds Ratio
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Transcription Factors / genetics*
  • Uncoupling Protein 2


  • DNA, Mitochondrial
  • Heat-Shock Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors
  • UCP2 protein, human
  • Uncoupling Protein 2