Haplotype of RNASE 3 polymorphisms is associated with severe malaria in an Indian population
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ORIGINAL ARTICLE
Haplotype of RNASE 3 polymorphisms is associated with severe malaria in an Indian population Benudhar Mukhi1,3 · Himanshu Gupta2 · Samuel C. Wassmer2 · Anupkumar R. Anvikar1 · Susanta Kumar Ghosh1,3 Received: 5 July 2020 / Accepted: 20 October 2020 © Springer Nature B.V. 2020
Abstract Severe malaria (SM) caused by Plasmodium falciparum (Pf) infection has been associated with life-threatening anemia, metabolic acidosis, cerebral malaria and multiorgan dysfunction. It may lead to death if not treated promptly. RNASE 3 has been linked to Pf growth inhibition and its polymorphisms found associated with SM and cerebral malaria in African populations. This study aimed to assess the association of RNASE 3 polymorphisms with SM in an Indian population. RNASE 3 gene and flanking regions were amplified followed by direct DNA sequencing in 151 Indian patients who visited Wenlock District Government Hospital, Mangalore, Karnataka, India. Allele, genotype and haplotype frequencies were compared between patients with SM (n = 47) and uncomplicated malaria (UM; n = 104). Homozygous mutant genotype was only found for rs2233860 (+ 499G > C) polymorphism ( A), rs2073342 (+ 371C > G) and rs2233860 (+ 499G > C) polymorphisms was correlated significantly with SM patients (OR = 3.03; p = 0.008) after Bonferroni correction. A haplotype of RNASE 3 gene was found associated with an increased risk of SM and confirming that RNASE 3 gene plays a role in susceptibility to SM. Keywords Severe malaria · RNASE 3 · Polymorphisms · ECP · Plasmodium falciparum
Introduction Malaria remains to be a major public health problem in low and middle-income countries, especially in the sub-Saharan region. The World Health Organization (WHO) estimated that 228 million cases of malaria and 405,000 related deaths occurred globally in 2018 [1]. 19 sub-Saharan African Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05934-1) contains supplementary material, which is available to authorized users. * Himanshu Gupta [email protected]; [email protected] 1
ICMR-National Institute of Malaria Research, New Delhi, India
2
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St. Bloomsbury, London WC1E 7HT, UK
3
Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
countries and India were responsible for carrying approximately 85% of the worldwide burden [1]. Plasmodium falciparum (Pf) malaria is a complex disease with a wide spectrum of clinical manifestations ranging from uncomplicated (UM) to severe malaria (SM). SM is defined by life-threatening anemia, metabolic acidosis, cerebral malaria (CM), and multiorgan system involvement [2]. Sequestration of Pf-parasitized erythrocytes within the microvasculature of vital organs in the human host is considered a key pathogenic event leading to SM [3, 4]. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is encode
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