Association of serum C-reactive protein level and polymorphisms with susceptibility to dengue infection and severe clini

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ORIGINAL INVESTIGATION

Association of serum C‑reactive protein level and polymorphisms with susceptibility to dengue infection and severe clinical outcome among eastern Indian patients Saikat Mukherjee1 · Anusri Tripathi1  Received: 28 February 2020 / Accepted: 18 July 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Dengue virus (DENV) infection is a major public health concern in India ranging from simple febrile illness to severe outcome. This study aimed to investigate association of serum CRP level and CRP gene polymorphisms towards development of dengue disease susceptibility and severity among eastern Indian patients. Blood was collected from 348 symptomatic patients. Sera was subjected to serological diagnosis for the presence of anti-dengue IgM, anti-dengue IgG antibodies and dengue NS1 antigen by ELISA. Viral RNA was extracted and the presence of DENV genome, viral load, serotypes was determined by qRT-PCR. CRP level and polymorphisms were determined by immunoturbidimetry and polymerase chain reaction–restriction fragment length polymorphism, respectively. Statistical analysis was performed by GraphPad-Prism. Among 206 dengue patients, CRP level increased significantly among patients within acute phase, and patients with qRTPCR/NS1 antigen positivity, high viral load (HVL), secondary infection, and DENV4 and DENV2 infections. rs3091244, TT genotype positively associated with dengue susceptibility (p = 0.03). CT genotype of rs3093059 and TT genotype of rs3091244 were found to correlate with elevated CRP level and development of WHO-defined warning signs. TT genotype of rs3091244 was more prevalent among HVL patients. Thus, these CRP polymorphic variants and CRP concentration might act as potential prognostic biomarkers for predicting disease severity among acute-stage dengue patients. Keywords  Dengue virus · WHO-warning signs · CRP · Polymorphism · Secondary dengue infection · Serotype

Introduction There has been rapid increase of dengue virus (DENV) infection in India during past decades [1]. This infection presents a wide spectrum of symptoms: simple dengue fever (DF), occasionally representing feverish illness, headache, joints and muscle pain, which matches with symptoms of other febrile illness, severe dengue involves haemorrhage,

Edited by Matthias J. Reddehase. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0043​0-020-00690​-2) contains supplementary material, which is available to authorized users. * Anusri Tripathi [email protected] 1



Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, 108, C. R. Avenue, Kolkata, West Bengal 700073, India

persistent vomiting, abdominal pain and severe plasma leakage [1–3]. Severe dengue has been associated with lifethreatening disease complications, patient mortality rate lying between 10 and 20% in case of patients with dengue haemorrhagic fever (DHF) and 40% among dengue shock syndrome (DSS) patients [4]. According to World Health Orga