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
| Autor: | S. K. Sharma, Shally Awasthi, Saman Habib, Sanjib Mohanty, Sudhanshu S. Pati, Kanika Kanchan, Saroj Kanta Mishra, Vimala Venkatesh |
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| Rok vydání: | 2015 |
| Předmět: |
Microbiology (medical)
Plasmodium falciparum Malaria Cerebral Protozoan Proteins India Nitric Oxide Synthase Type II Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Asian People Gene Frequency Risk Factors parasitic diseases Genotype medicine Odds Ratio SNP Humans Genetic Predisposition to Disease Allele Malaria Falciparum Haplotype General Medicine medicine.disease biology.organism_classification Infectious Diseases C-Reactive Protein Haplotypes Cerebral Malaria Immunology E-Selectin Thrombospondins Malaria |
| Zdroj: | European journal of clinical microbiologyinfectious diseases : official publication of the European Society of Clinical Microbiology. 34(10) |
| ISSN: | 1435-4373 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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