Complement Receptor 1 Variants Confer Protection from Severe Malaria in Odisha, India

<div><h3>Background</h3><p>In <em>Plasmodium falciparum</em> infection, complement receptor-1 (CR1) on erythrocyte’s surface and ABO blood group play important roles in formation of rosettes which are presumed to be contributory in the pathogenesis of severe malaria. Although several studies have attempted to determine the association of CR1 polymorphisms with severe malaria, observations remain inconsistent. Therefore, a case control study and meta-analysis was performed to address this issue.</p> <h3>Methods</h3><p>Common CR1 polymorphisms (intron 27 and exon 22) and blood group were typed in 353 cases of severe malaria (SM) [97 cerebral malaria (CM), 129 multi-organ dysfunction (MOD), 127 non-cerebral severe malaria (NCSM)], 141 un-complicated malaria and 100 healthy controls from an endemic region of Odisha, India. Relevant publications for meta-analysis were searched from the database.</p> <h3>Results</h3><p>The homozygous polymorphisms of CR1 intron 27 and exon 22 (TT and GG) and alleles (T and G) that are associated with low expression of CR1 on red blood cells, conferred significant protection against CM, MOD and malaria deaths. Combined analysis showed significant association of blood group B/intron 27-AA/exon 22-AA with susceptibility to SM (CM and MOD). Meta-analysis revealed that the CR1 exon 22 low expression polymorphism is significantly associated with protection against severe malaria.</p> <h3>Conclusions</h3><p>The results of the present study demonstrate that common CR1 variants significantly protect against severe malaria in an endemic area.</p> </div

Details of study participants.

<p>Note: Data are no. (%) of participants unless otherwise specified. UM; uncomplicated malaria, CM; cerebral malaria, MOD; multiorgan dysfunction, NCSM; non cerebral severe malaria, HC; healthy controls, NA; not applicable, NS; not significant.</p

Forest plots of CR1 intron 27 polymorphism in association to severe malaria.

<p>Meta-analysis was performed including previous reports and current study by comprehensive meta-analysis software. Random or fixed model of meta-analysis was employed for calculation of the combined effect of all studies. Forest plots evaluating resistance/risk factor of different models to severe malaria are shown.</p

Characteristics of all studies included in meta-analysis.

<p>NOTE: Data are no. (%) of participants unless otherwise specified. SM; severe malaria, MM; Mild malaria, SMA; severe malaria anemia, PNG; Papua New Guinea, RFLP; restriction fragment length polymorphisms, NA; not associated, ND; not done.</p

Association of combined blood groups and CR1 polymorphisms (intron 27 and exon 22) with <i>P. falciparum</i> malaria.

<p>NOTE: Data are no. (%) of participants unless otherwise specified. UM: uncomplicated malaria; CM: cerebral malaria; MOD: multi-organ dysfunction; NCSM: non-cerebral severe malaria; OR: odds ratio; CI: confidence interval.</p

Association of CR1 polymorphisms, ABO blood group in treatment outcome patients with severe malaria.

<p>NOTE: Data are no. (%) of participants unless otherwise specified. CM: cerebral malaria; MOD: multi-organ dysfunction; NCSM: non-cerebral severe malaria; UM: uncomplicated malaria; OR: odds ratio; CI: confidence interval.</p

Haplotype analysis of CR1polymorphisms in treatment outcome of <i>P. falciparum</i> malaria patients.

<p>NOTE: Data are shown in percentage. OR: odds ratio; CI: confidence interval.</p

Statistics to test publication bias and heterogeneity in meta-analysis.

<p>Statistics to test publication bias and heterogeneity in meta-analysis.</p

Haplotype analysis of CR1polymorphisms in <i>P. falciparum</i> malaria patients.

<p>NOTE: Data are shown in percentage. UM: uncomplicated malaria; CM: cerebral malaria; MOD: multi-organ dysfunction; NCSM: non-cerebral severe malaria; OR: odds ratio; CI: confidence interval.</p

Flow diagramme of identifying potential studies for meta-analysis.

<p>Flow diagramme of identifying potential studies for meta-analysis.</p