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Association of G84A and C276T polymorphism in neuronal nitric oxide synthase (nNOS) gene with herpes simplex encephalitis in eastern Indian population
Nitric Oxide ( IF 3.2 ) Pub Date : 2020-12-18 , DOI: 10.1016/j.niox.2020.12.007
S K Rathore 1 , P Pati 1 , S Priyadarshini 2 , B Dwibedi 3
Affiliation  

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.



中文翻译:

印度东部人群中神经元一氧化氮合酶 (nNOS) 基因 G84A 和 C276T 多态性与单纯疱疹脑炎的关联

在这项研究中,研究了一个假设,即神经元一氧化氮合酶 (nNOS) 的遗传变异可能影响单纯疱疹脑炎的易感性和结果。nNOS 基因、G84A 和 C276T 的多态性位点在来自奥里萨邦的相同种族背景的 132 例 HSE 病例(年龄 8.2 ± 1.3 岁)和 143 例健康个体(年龄 9.2 ± 1.6 岁)中进行了基因分型。HSVE 风险显着增加与 AG 基因型 (OR = 1.73, 95%CI = 1.03–2.9, P = 0.03) 和 AA 基因型 (OR = 2.96, 95%CI = 1.04–8.4, P = 0.04) 相关nNOS 84G →A 位点。在 nNOS 276C→T 变异的情况下,HSVE 风险与 CT 基因型(OR = 1.79,95%CI = 1.07–3.0,P = 0.03)和 TT 基因型(OR = 3.6,95%CI = 1.2–10.8,P = 0.02)。结果不佳的患者对于两种 SNP 均具有纯合或杂合基因型,但单独的基因型分析不能显示显着性。但是两个 SNP 的联合基因型分析证实 GG + CC 是导致不良结果的危险因素。(OR = 6.3,CI-1.9-20.7,P = 0.0033)。两种 SNP 的单倍型分析确实显示“at”单倍型显着更高,并且与 HSVE 病例相关(OR = 2.322,CI:1.43–3.77,P = 0.00070)。本研究中观察到的结果表明,nNOS 的这些位点的变异可能降低了其表达并导致 NO 的产生减少,这导致了 HSVE 的风险,但在这些患者中提供了良好的结果。两种 SNP 的单倍型分析确实显示“at”单倍型显着更高,并且与 HSVE 病例相关(OR = 2.322,CI:1.43–3.77,P = 0.00070)。本研究中观察到的结果表明,nNOS 的这些位点的变异可能降低了其表达并导致 NO 的产生减少,这导致了 HSVE 的风险,但在这些患者中提供了良好的结果。两种 SNP 的单倍型分析确实显示“at”单倍型显着更高,并且与 HSVE 病例相关(OR = 2.322,CI:1.43–3.77,P = 0.00070)。本研究中观察到的结果表明,nNOS 的这些位点的变异可能降低了其表达并导致 NO 的产生减少,这导致了 HSVE 的风险,但在这些患者中提供了良好的结果。

更新日期:2020-12-31
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