Inducible Nitric Oxide Synthase (iNOS) Gene Polymorphism and Disease Prevalence

Abstract

Nitric oxide synthase gene is present on chromosome 17 and has been implicated in a wide variety of diseases. The nitric oxide synthase enzyme forms nitric oxide that besides being a signalling molecule plays an important role in host immune response. Inducible nitric oxide synthase expression is regulated at the level of transcription. Single‐nucleotide polymorphisms, copy number variation and simple sequence repeat are important variations that have been reported in human genome. The presence of such variations in the regulatory region affects the level of gene product in the cell, while variation in the coding region influences the structure of proteins and its activity. This alteration in the level of gene product and the structure of the protein molecule might be responsible for the final outcome of genetic as well as infectious diseases. In the present manuscript, we review the role of inducible nitric oxide synthase (iNOS) gene polymorphisms in different diseases and populations. The iNOS gene with one pentanucleotide repeat, two single‐nucleotide polymorphisms in promoter region and one polymorphism in exon 16 has been implicated in several diseases. We have also predicted several polymorphisms in the promoter region of iNOS computationally, which might affect the transcription factor binding site (TFBS) and hypothesize that these polymorphisms have some putative role in the outcome of disease(s).

Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study

“…22 The functional role of iNOS (G/A-37498) polymorphism is not well known but it may alter NO activity. 16 The allelic variant of nNOS C/T in exon 29 is located in an untranslated region of the gene and may influence the rate of expression and stability of nNOS mRNA. 23 Studies on the association between NOS gene isoform polymorphisms and achalasia, however, are scanty.…”

“…11,12 The genes encoding for these isoforms are located in the human chromosomes 7q36, 17q11.2-q12, and, 12q24.2, respectively, which have several polymorphisms. 11,[13][14][15][16][17][18][19] Polymorphisms in eNOS, iNOS, and nNOS genes result in occurrence of either "high" or "low" producer alleles. Subjects homozygous for the high-producer alleles synthesize the highest amount of NO, those homozygous for the low-producer alleles the least, while heterozygotes produce an intermediate amount.…”

Genetic Determinants of Microvascular Complications in Type 1 Diabetes

“…It has been postulated that in diabetic kidney there is increased NO synthase (NOS) activity, and the excessive NO production can 9 induce the renal hyperfiltration and hyperperfusion and by its perturbing effect contributes to the DN appearance (Bazzaz et al, 2010). In early diabetes, the retinal circulation devoided of any extrinsic innervation and depending entirely on endothelium-mediated autoregulation, is dramatically affected by the ECs dysfunction due to the lack of the local NO, a state seen in DR (Qidwai & Jamal, 2010). In active progressive DR, aqueous NO levels are significantly high, while plasma NO levels remained at the level of diabetics without DR (Yilmaz et al, 2000).…”

Biomedical Importance of Host Genetic Factors in Infectious Diseases

“…It has been proposed that NO produced by tuberculosis-infected human macrophages and by epithelial cells is anti mycobacterial against M. tuberculosis . A report indicates that the alveolar macrophages from the lungs of patients with tuberculosis express NOS2A in potentially mycobactericidal amounts and this NOS2A can kill mycobacterium in vitro (Qidwai & Jamal, 2010). We have review the role of three SNPs (-954G/C, -1173C/T, -1659 A/T), one microsatellite repeat in promoter and one SNP in exon 16 of gene in several case control studies (Qidwai & Jamal, 2010).…”

“…A report indicates that the alveolar macrophages from the lungs of patients with tuberculosis express NOS2A in potentially mycobactericidal amounts and this NOS2A can kill mycobacterium in vitro (Qidwai & Jamal, 2010). We have review the role of three SNPs (-954G/C, -1173C/T, -1659 A/T), one microsatellite repeat in promoter and one SNP in exon 16 of gene in several case control studies (Qidwai & Jamal, 2010). The promoter polymorphisms (-954G/C, -1173C/T, -1659 A/T) have been shown to increase NO synthesis (Hobbs et al, 2002).…”