RESUMEN
Leprosy is a major health concern and continues to be a source of fear and stigma among people worldwide. Despite remarkable achievements in the treatment, understanding of pathogenesis and transmission, epidemiology of leprosy still remains inadequate. The prolonged incubation period, slow rates of occurrence in those exposed and deceptive clinical presentation pose challenges to develop reliable strategies to stop transmission. Hence, there is a need for improved diagnostics and therapies to prevent mortality caused by leprosy. The objectives of this study are to identify significant genes from protein-protein interactions (PPIs) network of leprosy and to choose the most effective therapeutic targets. Fifty genes related with leprosy were discovered by literature mining. These genes were used to construct a primary network. Leading Eigen Vector method was used to break down the primary network into various sub-networks or communities. It was found that the primary network was divided into many sub-networks at the 6 levels. Seed genes were traced at each level till key regulatory genes were identified. Three seed genes, namely, GNAI3, NOTCH1, and HIF1A, were able to make their way till the final motif stage. These genes along with their interacting partners were considered key regulators of the leprosy network. This study provides leprosy-associated key genes which can lead to improved diagnosis and therapies for leprosy patients.
RESUMEN
PURPOSE: Earlier studies have shown that tumor necrosis factor (TNF) -308 G>A (rs1800629) gene polymorphism is implicated in the susceptibility to leprosy, but results were inconsistent. METHODS: A meta-analysis of 14 studies involving 3327 leprosy cases and 3203 controls was performed to appraise the association of TNF -308 G>A polymorphism with leprosy using MEDLINE (PUBMED), EMBASE, and Google Scholar web databases. RESULTS: Overall, no significant association was observed in allelic (A vs. G: P=0.068; OR = 0.836, 95% CI = 0.689-1.013), homozygous (AA vs. GG: P=0.394; OR = 0.810, 95% CI = 0.499-1.315), heterozygous (GA vs. GG: P=0.059; OR = 0.780, 95% CI = 0.603-1.010), dominant (AA + GA vs. GG: P=0.067; OR = 0.797, 95% CI = 0.625-1.016), and recessive (AA vs. GG + GA: P=0.594; OR = 0.877, 95% CI = 0.542- 1.420) genetic models. Subgroup analysis showed no association in Asians. Whereas, reduced risk was found in allelic contrast (A vs. G: P=0.014; OR = 0.832, 95% CI = 0.718-0.963) and dominant models (AA + GA vs. GG: P=0.004; OR = 0.790, 95% CI = 0.673-0.928) of the mixed population. CONCLUSIONS: TNF -308 G>A polymorphism is not associated with leprosy risk in the overall population. However, subgroup analysis demonstrated protective effect of the said polymorphism in leprosy risk in the Latin American population, but showed no association in the Asians.