Genetics of Obesity, Insulin Resistance, Subcutaneous Fat, and Fatty Liver: Relationships of Apolipoproteins B, E, and C3 and PPAR-γ Gene Polymorphisms and Other Candidate Genes

  • Dr. Misra and his team were first to show the negative association of apolipoprotein-B gene polymorphisms with generalized and regional obesity for Asian Indians in India. Recently, they reported a strong association of apolipoprotein-E4 allele with early-onset of coronary heart disease.
  • They investigated genotype-phenotype correlations of peroxisome-proliferator receptor-α and γ genes with obesity, diabetes mellitus and hyperlipidemia in Asian Indians.
  • Studies of polymorphisms of 13 genes as genetic determinants of insulin resistance and subcutaneous body fat are ongoing.
  • d. Similarly, Dr. Misra and his team are also investigating the genetic association of fatty liver with peroxisome-proliferator receptor-α and γ genes.
  • Collaborative Studies with Department of Cardiology, University of Maryland: In collaboration with Dr. Mike Miller (University of Maryland, MD, USA), Dr. Misra has investigated polymorphisms of APOC3 promoter (C-482T,T-455C), APOE genotypes (2/3/4), PPAR alpha (intron 7: G/C), PPAR gamma (Pro12Ala), GNB3 (C825T and G814A), B3AR (Trp64Arg), FABP2 (Ala54Thr) and LPL (-93 T/G) in Asian Indians in India and Caucasians in USA. These data demonstrate that the prevalence of the metabolic syndrome was particularly elevated in homozygotes with the APOC3 promoter polymorphism variants (C-482T, T-455C) and raises the possibility that alterations in a single-gene may contribute to the metabolic syndrome.