iNOS polymorphism modulates iNOS/NO expression via impaired antioxidant and ROS content in P. vivax and P. falciparum infection.

Abstract

Nitric oxide (NO) has dicotomic influence on modulating host-parasite interplay, synchronizing physiological orchestrations and diagnostic potential; instigated us to investigate the plausible association and genetic regulation among NO level, components of oxidative stress, iNOS polymorphisms and risk of malaria. Here, we experimentally elucidate that iNOS promoter polymorphisms are associated with risk of malaria; employing mutation specific genotyping, functional interplay using western blot and RT-PCR, quantitative estimation of NO, total antioxidant content (TAC) and reactive oxygen species (ROS). Genotyping revealed significantly associated risk of P. vivax (adjusted OR = 1.92 and 1.72) and P. falciparum (adjusted OR = 1.68 and 1.75) infection with SNP at iNOS-954G/C and iNOS-1173C/T positions, respectively; though vivax showed higher risk of infection. Intriguingly, mutation and infection specific differential upregulation of iNOS expression/NO level was observed and found to be significantly associated with mutant genotypes. Moreover, P. vivax showed pronounced iNOS protein (2.4 fold) and mRNA (2.5 fold) expression relative to healthy subjects. Furthermore, TAC and ROS were significantly decreased in infection; and differentially decreased in mutant genotypes. Our findings endorse polymorphic regulation of iNOS expression, altered oxidant-antioxidant components and evidences of risk association as the hallmark of malaria pathogenesis. iNOS/NO may serve as potential diagnostic marker in assessing clinical malaria.

• Authors: Amod Kumar, Krishn Pratap Singh, Prerna Bali, Shadab Anwar, Asha Kaul, Om P Singh, Birendra Kumar Gupta, Nutan Kumari, Md Noor Alam, Mohammad Raziuddin, Manoranjan Prasad Sinha, Samudrala Gourinath, Ajay Kumar Sharma, Mohammad Sohail
• Journal: Redox biology (Redox Biol) Vol. 15 Pg. 192-206 (05 2018) ISSN: 2213-2317 [Electronic] Netherlands
• PMID: 29268202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Nitric Oxide
• Nitric Oxide Synthase Type II

Topics

• Adult
• Female
• Genotype
• Host-Parasite Interactions (genetics)
• Humans
• Malaria, Falciparum (genetics, metabolism, parasitology, pathology)
• Malaria, Vivax (genetics, metabolism, parasitology, pathology)
• Male
• Nitric Oxide (genetics, metabolism)
• Nitric Oxide Synthase Type II (genetics)
• Oxidative Stress (genetics)
• Plasmodium falciparum (genetics, metabolism, pathogenicity)
• Plasmodium vivax (genetics, metabolism, pathogenicity)
• Promoter Regions, Genetic
• Reactive Oxygen Species (metabolism)