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The prevalence and mortality due to multifactorial polygenic diseases; hypertension, coronary artery disease (CAD), diabetes and cancer vary depending upon genetic susceptibility and environmental precursors because they have identifiable mendelian subsets. Rapid changes in diet and lifestyle, may influence heritability of the variant phenotypes that are dependent on the nutraceutical or functional food supplementation for their expression. It is possible to recognize the interaction of specific nutraceuticals, with the genetic code possessed by all nucleated cells. There is evidence that South Asians have an increased susceptibility to CAD, diabetes mellitus, central obesity and insulin resistance at younger age, which may be due to interaction of gene and nutraceutical environment. These populations appear to have enherited predisposition and may have interaction of internal nutritional status and environmental factors. Higher intake of refined starches and sugar increases generation of super oxide anion in the leucocytes and mononuclear cells, and free fatty acids (FFA), as well as higher amount and activity of nuclear factor-kB (NF-kB), a transcriptional factor regulating the activity of at least 125 genes, most of which are pro-inflammatory. Glucose intake also causes an increase in two other proinflammatory transcription factors; activating protein-1 (AP-1) and early growth response protein-1 (Egr-1), the first regulating the transcription of matrix metallo-proteinases and the second modulating the transcription of tissue factor and plasminogen activator inhibitor-1. Refined food, mixed meal induces activation of NF-kB associated with free radicals …