Venous Thromboembolism (VTE) is a multifactorial disease that is influenced by individual genetic background and various environmental factors, high altitude (HA) being the one. HA exposure may cause release of several damage associated molecular patterns (DAMPs), which act as ligand for various immune receptors. Previous studies on western population involving SNPs analysis of TLRs demonstrated that TLRs are involved in development and progression of several cardiovascular diseases. But, no such study has been done in Indian population in context of HA exposure. TLRs, being receptors play a significant role in manifestation and elimination of diseases by recognition of specific ligands and downstream signal transduction therefore; the genetic variation in TLRs could be implicated for imparting varying response of individuals to discrete diseases.
Therefore, in accordance with it, in present study changes in protein structures of TLR2 and TLR4 due to presence of SNP were accessed by in-silico tools to observe whether the mutation has effect on protein structure and integrity which further influencing its function. The results showed that SNP harbouring protein has decreased functional pockets, thus may be protective for disease. Taking this lead further to genotypic level, first time association between Toll-like receptor genes polymorphism and risk of high altitude induced venous thrombosis is analyzed in Indian population by PCR RFLP method. Though the result showed initial trend that TLR2 and TLR9 SNP are monomrphic in distribution and for TLR4 there was no significant difference in distribution of SNP between healthy and HA-DVT group, these SNPs have potential to be used as susceptibility markers if studied in large population size.
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