Human Glutathione S-Transferase Enzyme Gene Polymorphisms and Their Association With Neurocysticercosis

Abstract

Neurocysticercosis (NCC), caused by cysticerci of Taenia solium is the most common helminthic infection of the central nervous system. Some individuals harboring different stages of cysticerci in the brain remain asymptomatic, while others with similar cysticerci lesions develop symptoms and the reasons remain largely unknown. Inflammatory response to antigens of dying parasite is said to be responsible for symptomatic disease. Reactive oxygen species (ROS) that are generated in inflammatory conditions can damage cellular macromolecules such as lipids, DNA, and proteins. The glutathione S-transferases (GSTs) are critical for the protection of cells from ROS. A total of 250 individuals were included in the study: symptomatic NCC = 75, asymptomatic NCC = 75, and healthy controls = 100. The individuals carrying the deletions of GSTM1 and GSTT1 were at risk for NCC (OR = 2.99, 95 %CI = 1.31-6.82, p = 0.0073 and OR = 1.94, 95 %CI = 0.98-3.82, p = 0.0550 respectively). Further, the individuals with these deletions were more likely to develop symptomatic disease (OR = 5.08, 95 % CI = 2.12-12.18, p = 0.0001 for GSTM1 and OR = 3.25, 95 %CI = 1.55-6.82, p = 0.0018 for GSTT1). Genetic variants of GSTM3 and GSTP1 were not associated with NCC. The total GST activity and levels of GSTM1, GSTT1, and GSTM3 were significantly higher in asymptomatic subjects than in symptomatic and healthy controls. Lower GST activity was observed in individuals with GSTM1 and GSTT1 deletions. The present study suggests that the individuals with GSTM1 and GSTT1 deletions are at higher risk to develop symptomatic disease. The higher GST activity and levels of GSTM1, GSTT1, and GSTM3 are likely to play role in maintaining asymptomatic condition.

Long-Term Phenotypic and Proteomic Changes Following Vitrified Embryo Transfer in the Rabbit Model

“…Besides, we found upregulation in four DEPs ( GSTM2, LOC100357148, ADH2-1, EPHX1 ) related to the detoxification mechanisms of cytochrome P450, with the first two having glutathione transferase activity. Glutathione transferase activity is one of the main cellular mechanisms to tackle the damage from reactive oxygen species and, together with the P450 enzymes, are involved in the hepatic drug metabolism pathways [ 61 , 62 ]. Then, the upregulation of these proteins could be indicative of high hepatic detoxification requirements in an organism with oxidative metabolic disturbances.…”

Neurocysticercosis Burden in Pig Farming Community of North India

“…The study suggests that the individuals with GSTM1 and GSTT1 deletions are at higher risk to develop symptomatic disease because such individuals have low level of GSTs that fail to protect tissues from ROS related oxidative damage. The higher GST activity and levels of GSTM1, GSTT1, and GSTM3 are likely to protect tissue from oxidative damage thus maintaining asymptomatic condition (36).…”