Over the last decade, we have demonstrated that spectrum of genetic variants and their interaction with various environmental factors including micronutrients that influences complex diseases such as Chronic Pancreatitis, Type 2 Diabetes and Neural Tube Defects is different in Indians. Thus, genetic screening tests used for these diseases in the Europeans and Americans may not be helpful for risk prediction in Indians. 
Here are some of our key findings:

  • We have established that rather than a nutritional disease, Tropical Calcific Pancreatitis (TCP) is a genetic disease (OMIM: 608189) and its genetic basis is different compared to Caucasians. We also identified Cathepsin B as a novel susceptibility gene for TCP and postulate that rather than trypsinogen gene mutations, screening for mutations in SPINK1 (OMIM: 167790) & Cathepsin B (OMIM: 116810) genes may be more useful for genetic testing of chronic pancreatitis in Indians.
  • Contrary to maternal folate deficiency or methylene tetra hydrofolate reductase gene (MTHFR) polymorphisms predicting susceptibility to Neural Tube Defects (NTDs) in western population, we demonstrated that B12 deficiency and transcobalamin (TCN2) polymorphisms predict susceptibility to NTDs in Indian population. Thus, B12 supplementation should be added to the recommendation of peri-conceptional folate supplementation for prevention of occurrence and recurrence of NTD children being born to Indian pregnant women.
  • We have provided evidence of existence of thiamine deficiency in several rural sectors of Andhra Pradesh and  demonstrated that persistent thiamine deficiency leads to acute life-threatening presentation of Leigh syndrome in neonates and infants. The observation suggests caution and a role for timely thiamine supplementation for prevention of untimely deaths of such children. 
  • We demonstrated that FTO variants do not entirely mediate the risk of diabetes through obesity in Indians, which was further confirmed in other populations world-wide. Further, genome-wide association study in Western Indians have identified 2 novel loci, influencing obesity and insulin secretion to be strongly associated with type 2 diabetes in Indians.  
  • Through Mendelian Randomization analysis using homocysteine raising MTHFR variants, we have established a causal role for high homocysteine levels (due to imbalance in maternal folate/B12 levels) in fetal programming of birth weight, obesity and insulin resistance which are established intermediate risk traits for future development of   cardio-metabolic syndrome.

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