title: CR1 levels and gene polymorphisms exhibit differential association with falciparum malaria in regions of varying disease endemicity.
abstract: Complement receptor 1 (CR1/CD35) levels on erythrocytes and related CR1 polymorphisms have been associated with response to falciparum malaria in populations inhabiting malaria-endemic regions. Differences in disease association profiles of its low expression alleles have been observed in populations from different regions of the world. We analyzed the influence of CR1 levels and associated SNPs on susceptibility/resistance to falciparum malaria in Indian populations. Two CR1 SNPs [exon 22 (A/G) and intron 27 (A/T)] define the low expression (L) CR1 allele in populations inhabiting a Plasmodium falciparum-endemic and a nonendemic region of India. Populations of the endemic region have very low red blood cell surface CR1 levels and higher frequencies of the exon 22 and intron 27 mutant L alleles. Whereas low CR1 levels correlated with susceptibility to severe malaria in the nonendemic region, high CR1 levels were associated with manifestation of disease in the endemic region. In addition, the exon 22 L allele was a risk factor for severe malaria in the nonendemic region. Absence of correlation between levels of tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 with CR1 levels in patients with severe disease indicated that RBC CR1 levels in individuals are not the major determinants of pro-inflammatory cytokine release during infection. Our results are interpreted in the context of differences in the pathogenesis of severe malaria in the malaria-endemic and nonendemic region.
authors.affiliation: Division of Molecular and Structural Biology, Central Drug Research Institute, Lucknow, India.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Sinha
authors.forename: Ganga N
authors.initials: GN
authors.lastname: Jha
authors.forename: Prerna
authors.initials: P
authors.lastname: Anand
authors.forename: Tabish
authors.initials: T
authors.lastname: Qidwai
authors.forename: Sudhanshu S
authors.initials: SS
authors.lastname: Pati
authors.forename: Sanjib
authors.initials: S
authors.lastname: Mohanty
authors.forename: Saroj K
authors.initials: SK
authors.lastname: Mishra
authors.forename: Prajesh K
authors.initials: PK
authors.lastname: Tyagi
authors.forename: Surya K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Vimala
authors.initials: V
authors.lastname: Venkatesh
authors.forename: Saman
authors.initials: S
authors.lastname: Habib
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D019353:Endemic Diseases; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017463:Receptors, Complement 3b / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D017463:Receptors, Complement 3b