caa a22 4500 606156844 CHVBK 20210128100610.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s10096-015-2448-0 doi (NATIONALLICENCE)springer-10.1007/s10096-015-2448-0 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 [Elektronische Daten] [K. Kanchan, S. Pati, S. Mohanty, S. Mishra, S. Sharma, S. Awasthi, V. Venkatesh, S. Habib] 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. Springer-Verlag Berlin Heidelberg, 2015 Kanchan K. Division of Molecular and Structural Biology, CSIR—Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, 226031, Lucknow, India aut Pati S. Ispat General Hospital, Rourkela, India aut Mohanty S. Ispat General Hospital, Rourkela, India aut Mishra S. Ispat General Hospital, Rourkela, India aut Sharma S. National Institute of Malaria Research, New Delhi, India aut Awasthi S. King George's Medical University, Lucknow, India aut Venkatesh V. King George's Medical University, Lucknow, India aut Habib S. Division of Molecular and Structural Biology, CSIR—Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, 226031, Lucknow, India aut European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/10(2015-10-01), 2029-2039 0934-9723 34:10<2029 2015 34 10096 https://doi.org/10.1007/s10096-015-2448-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10096-015-2448-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kanchan K. Division of Molecular and Structural Biology, CSIR—Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, 226031, Lucknow, India aut NATIONALLICENCE 700 1- Pati S. Ispat General Hospital, Rourkela, India aut NATIONALLICENCE 700 1- Mohanty S. Ispat General Hospital, Rourkela, India aut NATIONALLICENCE 700 1- Mishra S. Ispat General Hospital, Rourkela, India aut NATIONALLICENCE 700 1- Sharma S. National Institute of Malaria Research, New Delhi, India aut NATIONALLICENCE 700 1- Awasthi S. King George's Medical University, Lucknow, India aut NATIONALLICENCE 700 1- Venkatesh V. King George's Medical University, Lucknow, India aut NATIONALLICENCE 700 1- Habib S. Division of Molecular and Structural Biology, CSIR—Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, 226031, Lucknow, India aut NATIONALLICENCE 773 0- European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/10(2015-10-01), 2029-2039 0934-9723 34:10<2029 2015 34 10096