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Polymorphisms in host genes encoding NOSII, C-reactive protein, and adhesion molecules thrombospondin and E-selectin are risk factors for Plasmodium falciparum malaria in India

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Abstract

Cytoadherence of Plasmodium falciparum-infected red blood cells (RBCs) in host microvasculature and complex regulation of the immune response are important contributors to the clinical outcome of disease. We tested the association of 23 single nucleotide polymorphisms (SNPs) and a microsatellite repeat in adhesion molecule genes THBS1 and ESEL, and immune regulatory molecule genes NOSII, CRP, and MBL2 with falciparum malaria in populations residing in a malaria-endemic and a non-endemic region of India. The THBS1 haplotype CCCCA (rs1478604, rs7170682, rs2664141, rs12912082, rs3743125) was a risk factor in the endemic region (relative risk = 3.78) and an ESEL SNP (rs5368, His468Tyr) associated with cerebral malaria (CM) [CM vs. non-cerebral malaria (NCM), odds ratio (OR) = 2.23, p = 0.03]. In the non-endemic region, an ESEL 3′UTR SNP (rs5359) associated with enhanced risk of disease (OR = 3.62, p = 1 × 10−4) and the CT genotype of the CRP promoter SNP (C/T/A) strongly associated with protection (severe vs. control, OR = 0.29, p = 6 × 10−5). Long repeat alleles of the NOSII promoter microsatellite (CCTTT)n exhibited strong association with protection and the NOSII ATG haplotype (rs3729508, rs2297520, rs9282801) was strongly protective against severe malaria in both regions (endemic, severe vs. control, OR = 0.05, p = 0.0001; non-endemic, severe vs. control, OR = 0.3, p = 1 × 10−5). Our results suggest differential contribution of variants of the investigated genes in determining the outcome of malaria in Indian populations.

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Acknowledgments

We are grateful to all donors and their families. KK received a Senior Research Fellowship from the Council of Scientific and Industrial Research, Government of India. This work was funded by a grant to SH and VV from the Department of Biotechnology, Government of India (BT/PR6065/MED/14/738/2005) and the CSIR network project BSC0104i to SH. This is CDRI communication number 9019.

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The authors declare no conflict of interest.

Compliance with ethical standards

Ethical clearance for sample collection and approval of protocols was obtained from the Institutional Ethics Committee (Human Research) of participating institutes/hospitals. Informed written consent was obtained from each volunteer/guardian prior to the collection of blood samples.

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Correspondence to S. Habib.

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Kanchan, K., Pati, S.S., Mohanty, S. et al. Polymorphisms in host genes encoding NOSII, C-reactive protein, and adhesion molecules thrombospondin and E-selectin are risk factors for Plasmodium falciparum malaria in India. Eur J Clin Microbiol Infect Dis 34, 2029–2039 (2015). https://doi.org/10.1007/s10096-015-2448-0

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