High CR1 level and related polymorphic variants are associated with cerebral malaria in eastern-India

Rout, Ronnaly; Dhangadamajhi, Gunanidhi; Mohapatra, Biswajit; Kar, Shantanu Kumar; Ranjit, Manoranjan

doi:10.1016/j.meegid.2010.09.009

Cited by 18 publications

(30 citation statements)

References 16 publications

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“…Due to the habitats and hunter-gatherer lifestyle, all three Orang Asli groups are routinely exposed to medical stresses including malnutrition and persistent exposure to communicable diseases such as leptospirosis, smallpox, and of notably, malaria (Baer et al 1976;Eng et al 1973;Wee et al 2008;Bellwood 2007, page 256). Malaria exerts one of the strongest known evolutionary pressures on the human genome, giving rise to common Mendelian diseases such as sickle-cell disease, thalassemia and glucose-6-phosphatase dehydrogenase (G6PD) deficiency that paradoxically protect against malaria parasitic invasion (Clark et al 2009;Hanchard et al 2007;Kwiatkowski and Luoni 2006;Panda et al 2012;Rout et al 2011;Ruwende et al 1995). In addition to the range of genetic alterations influencing erythrocyte phenotypes such as haemoglobinopathies, reduced rosetting and reduced parasitic growth, malaria resistance can arise through other biological mechanisms that alter the structural and regulatory variation of globin genes or control the degree of oxidative stress from parasite invasion (Kwiatkowski 2005).…”

Section: Introductionmentioning

confidence: 99%

Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia

Liu

Yunus

et al. 2015

Hum Genet

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The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.

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Section: Introductionmentioning

confidence: 99%

Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia

Liu

Yunus

et al. 2015

Hum Genet

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“…A higher prevalence of the CR1 intron 27 minor allele has been reported in various malaria endemic areas viz., Thailand34 and India19 25 while in non-endemic areas, their frequency has also been found to be significantly low 2636 The other CR1 variant (exon 22) also showed a similar pattern: higher frequency of variants in endemic populations like Papua New Guinea,26 Thailand,34 India19 25 and lower prevalence in non-endemic areas 2526 Similarly, the minor allele of the exon 33 polymorphism is more frequent in malaria endemic than non-endemic areas 26.…”

Section: Discussionmentioning

confidence: 87%

“…Several single nucleotide polymorphisms (SNPs) have been reported in both coding and non-coding regions of the CR1 gene (ID 1378), but limited number of SNPs have functional relevance. The association of three common SNPs (intron 27: rs11118133, exon 22: rs2274567 and exon 33: rs3811381) have been well investigated in Plasmodium falciparum malaria18 19 and autoimmune disorders20 21 since they are believed to be associated with CR1 expression. CR1 seems to play an important role in pathogenesis of P. falciparum malaria by facilitating rosetting, a phenomenon by which plasmodium infected red blood cells (RBCs) bind to uninfected RBCs 22.…”

Section: Introductionmentioning

confidence: 99%

CR1 exon variants are associated with lowered CR1 expression and increased susceptibility to SLE in aPlasmodium falciparumendemic population

2016

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BackgroundComplement receptor 1 (CR1) plays an important role in immune complex clearance by opsonisation and possibly protects subjects from development of autoantibodies. Lower CR1 expression has been associated with susceptibility to systemic lupus erythematosus (SLE). In contrast, subjects displaying lower CR1 expression are protected against severe manifestations of falciparum malaria. This study is the first of its kind to investigate the association of CR1 variants with development of SLE in a P. falciparum endemic population from Odisha, India.MethodsCR1 polymorphisms (intron 27 (A>T), exon 22 (A>G) and exon 33 (G>C)) were typed by PCR and restriction length polymorphism in 297 cases of female patients with SLE and 300 age-matched and sex-matched healthy controls from malaria endemic areas in Odisha, India. CR1 expression on monocytes was quantified by flow cytometry.ResultsThe homozygous mutants of CR1 exon 22 (GG) and exon 33 (GG) and their minor alleles were associated with susceptibility to SLE. Furthermore, patients with SLE who harboured the GG genotype of the exon 33 polymorphism had a 3.12-fold higher chance of developing lupus nephritis. CR1 exon (22 and 33) variants were associated with lowered CR1 expression on monocytes in patients with SLE and in healthy controls. Patients with lupus nephritis showed significantly diminished CR1 expression than those without renal involvement (p=0.01).ConclusionsThe results of the present study demonstrate that common CR1 exon variants are associated with diminished CR1 expression on monocytes and increased susceptibility to development of SLE and lupus nephritis in a malaria endemic area.

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“…In disagreement with this finding, in Thailand two reports showed that low CR1 densities (homozygotes for LL) are not associated with protection from severe disease forms (Nagayasu et al, 2001;Teeranaipong et al, 2008). Several other studies further contribute to this discrepancy between reports (Fowkes et al, 2008;Kosoy et al, 2011;Lin et al, 2010;Panda et al, 2012;Rout et al, 2011;Sinha et al, 2009). Overall, no general rules can be proposed whether or not CR1 density on erythrocytes protects from malaria pathologies.…”

Section: Cr1 Expression Polymorphismmentioning

confidence: 95%

More than just immune evasion: Hijacking complement by Plasmodium falciparum

Schmidt

Kennedy

Tham

2015

Molecular Immunology

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High CR1 level and related polymorphic variants are associated with cerebral malaria in eastern-India

Cited by 18 publications

References 16 publications

Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia

Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia

CR1 exon variants are associated with lowered CR1 expression and increased susceptibility to SLE in aPlasmodium falciparumendemic population

More than just immune evasion: Hijacking complement by Plasmodium falciparum

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