FoxP3 gene expression and its genetic variants in scrub typhus infection

Abstract

Background: Scrub typhus, caused by a gram negative intracellular bacteria-Orientia tsutsugamushi is one of the re-emerging diseases and a major public health problem in Southeast Asian countries. Limited studies indicate a decrease in T-regulatory cells in scrub typhus infected patients. Fork-head box protein-3 (FoxP3) plays an important role in development and functioning of T-regulatory cells. Studies have highlighted the importance of FoxP3 expression and its polymorphism towards susceptibility to many infectious diseases. In the present study, we analyzed expression of FoxP3 and its possible association with the most widely studied gene polymorphism (FoxP3-924 A > G) among scrub typhus infected patients. Methods and materials: This case-control (67 cases, 71 healthy controls) study was conducted in Assam, India. Distribution pattern of −924 A > G (rs2232365) on the promoter of FoxP3 gene was evaluated using amplification-refractory mutation system- polymerase chain reaction (ARMS-PCR). Gene expression mRNA level was calculated by ‘2−ΔΔCT’ method using real time PCR. Student t-test and multinomial logistic regression analysis was performed for comparison. All statistical analysis was conducted using SPSS software. Results: FoxP3 gene expression was found to be significantly higher in cases compared to healthy controls (p < 0.05). mRNA levels of FoxP3 among cases was expressed at 17.76-fold higher than controls. Additionally, it was found that cases with AG genotype expressed FoxP3 at 5.64-fold higher than other two genotypes (p < 0.05). No significant effect of age and gender was noted in gene expression and genetic variants. Conclusion: The findings indicated a marked increase in FoxP3 expression in acute scrub typhus infection, which is contrary to a previous study. Further, it was found that individuals with rs2232365AG genotype are more susceptible to scrub typhus. It is therefore suggestive to conduct further studies to confirm the role of FoxP3 in scrub typhus infection.