Association of G84A and C276T polymorphism in neuronal nitric oxide synthase (nNOS) gene with herpes simplex encephalitis in eastern Indian population

• Published in: Nitric oxide 2021-03, Vol.108, p.8-11
• Main Authors: Rathore, S.K., Pati, P., Priyadarshini, S., Dwibedi, B.
• Format: Article
• Language: English
• Subjects: Herpes simplex encephalitis; nNOS; Outcome; Polymorphism
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2020.12.007

In this study, a hypothesis that genetic variations in neuronal nitric oxide synthase (nNOS) could influence the susceptibility and outcome of herpes simplex encephalitis was investigated. Polymorphic loci of nNOS gene, G84A and C276T were genotyped in 132 HSE cases (Age 8.2 ± 1.3yr) and 143 in healthy individuals (Age-9.2 ± 1.6yr) of the same ethnic background from Odisha. A significantly increased risk for HSVE was associated with the AG genotype (OR = 1.73, 95%CI = 1.03–2.9, P = 0.03) and AA genotype (OR = 2.96, 95%CI = 1.04–8.4, P = 0.04) of nNOS 84G →A locus. In case of nNOS 276C→T variation, HSVE risk was linked to CT genotype (OR = 1.79, 95%CI = 1.07–3.0, P = 0.03) and TT genotype (OR = 3.6, 95%CI = 1.2–10.8, P = 0.02). Patients with poor outcome either had homo or heterozygous genotype for both SNPs, but separate genotype analysis could not show significance. But combined genotype analysis of both SNPs confirmed that GG + CC was a risk factor for development of poor outcome. (OR = 6.3, CI-1.9-20.7, P = 0.0033). Haplotype analysis of both SNP did show that “at” haplotype was significantly higher and associated with HSVE cases (OR = 2.322,CI: 1.43–3.77, P = 0.00070). The result observed in this study suggested that variation at these loci of nNOS may have decreased its expression and caused low production of NO, which have resulted in risk of HSVE but provided good outcome in these patients. •We performed SNP analysis of NOS-1 gene to understand its role in herpes simplex encephalitis (HSE).•Risk of HSE was found with variants for both rs41279104 and rs 2682826 that results in low level of neuronal nitric oxide.•Poor outcome was linked with GG+CC,suggesting basal level of NO may cause poor outcome.•“at” haplotype was highly significant and associated with HSE.•Low production of NO due to variation of NOS-1 loci might have caused HSE but provided good outcome in these patients.