Association of polymorphisms in serotonin and nitric oxide genes with clinical outcome of dengue in Brazilian northeast population

• Published in: Acta tropica 2019-02, Vol.190, p.144-148
• Main Authors: dos Santos, Ana Caroline Melo, de Moura, Edilson Leite, da Silva, Denise Macêdo, Araujo Moura, Alexandre Wendell, Ferreira, Jean Moises, Lira Neto, Abel Barbosa, Pereira e Silva, Aline Cristine, de Medeiros Alves, Verônica, Balliano, Tatiane Luciano, de Farias, Karol Fireman, de Lima Filho, José Luiz, de Souza Figueiredo, Elaine Virgínia Martins
• Format: Article
• Language: English
• Subjects: Interferon-gamma; Nitric oxide; Polymorphism; Protection; Serotonin; Susceptibility
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2018.11.015

Serotonin (5HT) actively participates during platelet activation causing platelet aggregation and vasoconstriction. In addition, serotonin acts as a stimulant effect on the endothelium leading to the activation of the ENOS present in these cells consequently producing nitric oxide generating relaxation of the blood vessel in an attempt of physiological compensation. In addition, nitric oxide, once in the vascular lumen, binds platelets inhibiting platelet aggregation as it causes sequestration of calcium responsible for the stimulation of thromboxane A2 production responsible for platelet aggregation and vasoconstriction. Interferon gamma (INF GAMMA) that acts by inducing indoleamine 2,3 dioxygenase (IDO) contributing to lower levels of serotonin, also active to argininosuccinate (ASS) for the formation of l-arginine used as a substrate for the synthesis of Nitric Oxide. [Display omitted] •Polymorphisms in serotonin and nitric oxide genes have a role in the outcome of dengue.•Genotype SL for the 5-HTTLPR polymorphism was associated with protection against DHF.•Genotype GT of the SNP rs1799983 ENOS was associated with protection for DHF. Serotonin and nitric oxide seem to be involved in Dengue virus infection. The aim of this study was to investigate if SNPs in serotonin and nitric oxide are associated with dengue severity. A retrospective case-control study was conducted, with groups of dengue fever (DF; n = 78) and dengue hemorrhagic fever patients (DHF; n = 49). Genotyping was performed using qPCR and PCR. The power of the sample size was calculated by G*power software. The heterozygous SL for 5-HTTLPR SNP was significantly correlated with protection against progression to DHF in the codominant SS/SL/LL (OR = 0.22, 95% CI = 0.06–0.81, p = 0.011) and overdominant models SL vs SS + LL (OR = 0.19, 95% CI = 0.06–0.65, p = 0.003). For the ENOS (rs1799983) SNP, the genotype GT was positively associated with protection for development of the clinical form in DHF compared to dengue fever (OR = 0.39, 95% CI = (0.13–1.14), p = 0.0058) in codominant GG/GT/TT and overdominant model GT vs GG + TT (OR = 0.35, 95% CI = (0.12–1.02), p = 0.04). To our knowledge, this is the first study to identify the association of the serotonin and nitric oxide SNPs with dengue severity.