Rheumatic heart disease (RHD) is a post streptococcal autoimmune disease which generally affects the heart valves of young adults. The pathogenesis of RHD is complex and not clearly understood, however, various genetic and environmental factors are believed to play a crucial role in RHD causation. Here, an attempt was made to analyze the proinflammatory, adhesion, and gene expression and their promoter methylation in the mitral valves of RHD patients which were correlated with environmental factors such as housing, mode of cooking, nutritional status etc. We observed that all proinflammatory cytokines showed significant upregulation except TNF, highlighting the cogent localized inflammatory process in the mitral valves of RHD patients versus the mitral valves from healthy controls. Moreover, a significant upregulation of adhesion molecules (ICAM1, VCAM1, and E selectin) and cytoskeletal proteins (vimentin and laminin) were also documented in RHD group denoting the cytoskeletal remodeling in the mitral valves. Interestingly, we observed a significant association between IL1B and smoker in family and vimentin in patients staying in kaccha (mud) houses. On the other hand, promoter region of proinflammatory cytokines such as IL6, TNF, IL8, ICAM1 and laminin B were hypomethylated compared to healthy controls. However, we could not establish the association between environmental factors and promoter methylation. Thus, it can be attributed that in RHD high expression of proinflammatory as well as adhesion and cytoskeletal genes might be due to hypomethylation of their respective promoter which ultimately results valvular pathology and loss of valvular function.