Executive Summary : | Myositis, an inflammatory muscle disease, is caused by infection, injury, autoimmune conditions, smoking, and sometimes due to vitamin D deficiency. Pro-inflammatory cytokines such as TNF alpha, Il-6 play central roles in the pathogenesis of myositis. TNF alpha not only promotes muscular inflammation by itself but also by inhibiting an anti-inflammatory protein PPAR gamma. In addition to causing inflammation, TNF alpha also leads to muscle degeneration by upregulating the transcript level of Atrogin and MuRF1 which cause muscle protein degradation. Reactive oxygen species (ROS) also contributes to the development of myositis by increasing the level of TNF alpha. Production of TNF alpha is also upregulated by an intracellular ROS scavenger, PRDX1, which in addition to intracellular ROS scavenging, is secreted in the extracellular milieu, binds to membrane TLR4 and induces the production of IL-1/IL-6 and TNF-alpha. Another major contributor to myositis is mitochondrial dysfunction. PGC-1α, a transcriptional coactivator of PPARs, plays a key role in mitochondrial biogenesis and function, and additionally has anti-inflammatory effects. The interrelation between these aforesaid metabolic genes indicates their possible contribution in the pathogenesis of myositis. However, a comprehensive study on these genes in relation to myositis is missing. In the present study we hypothesized that the genetic variants of TNF alpha, IL-6, PPAR gamma, PGC-1alpha, PRDX1, FBXO32 and TRIM 63 genes may modulate the risk of myositis. Therefore, the present study is aimed to explore the role of the genetic variants of these metabolic genes on the risk of myositis. In addition, the genotypes of TNF alpha and IL-6 will also be correlated with serum level of TNF alpha and IL-6 so that genotypes of these genes can be used as susceptibility markers for this disease. |