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

• Published in: Redox biology Vol. 15; no. C; pp. 192 - 206
• Main Authors: Kumar, Amod, Singh, Krishn Pratap, Bali, Prerna, Anwar, Shadab, Kaul, Asha, Singh, Om P., Gupta, Birendra Kumar, Kumari, Nutan, Noor Alam, Md, Raziuddin, Mohammad, Sinha, Manoranjan Prasad, Gourinath, Samudrala, Sharma, Ajay Kumar, Sohail, Mohammad
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018; Elsevier
• Subjects: Adult; Female; Genotype; Host-Parasite Interactions - genetics; Humans; iNOS polymorphism; Jharkhand; Malaria, Falciparum - genetics; Malaria, Falciparum - metabolism; Malaria, Falciparum - parasitology; Malaria, Falciparum - pathology; Malaria, Vivax - genetics; Malaria, Vivax - metabolism; Malaria, Vivax - parasitology; Malaria, Vivax - pathology; Male; Nitric Oxide - genetics; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; NOS expression; Oxidative Stress - genetics; Plasmodium falciparum - genetics; Plasmodium falciparum - metabolism; Plasmodium falciparum - pathogenicity; Plasmodium vivax; Plasmodium vivax - genetics; Plasmodium vivax - metabolism; Plasmodium vivax - pathogenicity; Promoter Regions, Genetic; Reactive Oxygen Species - metabolism; Research Paper; ROS; SNP; Jharkhand; Plasmodium vivax; NOS expression; iNOS polymorphism; SNP; ROS
• DOI: 10.1016/j.redox.2017.12.005
• ISSN: 2213-2317

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. [Display omitted] •Polymorphism of iNOS revealed significantly associated risk of P. vivax and P. falciparum malaria and vivax showed higher risk of infection.•We observed mutation and infection specific differential expression of iNOS/NO cascade.•We investigated mutation specific antioxidant and ROS orchestration and observed lower TAC and ROS content in infection.•Evaluated the clinical correlation among stratified axillary temperature, NO and haemoglobin content during infection.