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Published on: December 4, 2015
Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India
Swapnil Sinha1, Tabish Qidwai, Kanika Kanchan
1Division of Molecular and Structural Biology, Central Drug Research Institute, Post box 173, Chattar Manzil, Mahatma Gandhi Marg, Lucknow-226001, India. swaps.gene@gmail.com
Background:
Host adhesion molecules play a significant role in the pathogenesis of Plasmodium falciparum malaria and changes in their structure or levels in individuals can influence the outcome of infection. The aim of this study was to investigate the association of SNPs of three adhesion molecule genes, ICAM1, PECAM1 and CD36, with severity of falciparum malaria in a malaria-endemic and a non-endemic region of India.
Methods:
The frequency distribution of seven selected SNPs of ICAM1, PECAM1 and CD36 was determined in 552 individuals drawn from 24 populations across India. SNP-disease association was analysed in a case-control study format. Genotyping of the population panel was performed by Sequenom mass spectroscopy and patient/control samples were genotyped by SNaPshot method. Haplotypes and linkage disequilibrium (LD) plots were generated using PHASE and Haploview, respectively. Odds-ratio (OR) for risk assessment was estimated using EpiInfotrade mark version 3.4.
Results:
Association of the ICAM1 rs5498 (exon 6) G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively). The CD36 rs1334512 (-53) T allele as well as the TT genotype associated with protection from severe disease (severe versus control, TT versus GG, OR = 0.37, P = 0.004). Interestingly, a SNP of the PECAM1 gene (rs668, exon 3, C/G) with low minor allele frequency in populations of the endemic region compared to the non-endemic region exhibited differential association with disease in these regions; the G allele was a risk factor for malaria in the endemic region, but exhibited significant association with protection from disease in the non-endemic region.
Conclusion:
The data highlights the significance of variations in the ICAM1, PECAM1 and CD36 genes in the manifestation of falciparum malaria in India. The PECAM1 exon 3 SNP exhibits altered association with disease in the endemic and non-endemic region.
Insights
Genetic variations in ICAM1, PECAM1, and CD36 influence Plasmodium falciparum malaria severity. Specific SNPs in ICAM1 and CD36 increase malaria risk, while others offer protection, with PECAM1 showing region-dependent effects.
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Host adhesion molecules are crucial in Plasmodium falciparum malaria pathogenesis.
- Genetic variations in these molecules can affect infection outcomes.
Purpose of the Study:
- To investigate the association of Single Nucleotide Polymorphisms (SNPs) in ICAM1, PECAM1, and CD36 genes with falciparum malaria severity.
- To compare these associations in malaria-endemic and non-endemic regions of India.
Main Methods:
- Genotyping of seven selected SNPs in ICAM1, PECAM1, and CD36 across 552 individuals from 24 Indian populations.
- Case-control study design for SNP-disease association analysis.
- Utilized Sequenom mass spectroscopy and SNaPshot for genotyping, PHASE for haplotypes, Haploview for LD plots, and EpiInfo for Odds Ratio estimation.
Main Results:
- The ICAM1 rs5498 (exon 6) G allele and CD36 exon 1a A allele were associated with increased severe malaria risk (OR=1.91, P=0.02; OR=2.66, P=0.0012).
- The CD36 rs1334512 (-53) T allele/genotype showed protection against severe malaria (OR=0.37, P=0.004).
- PECAM1 rs668 (exon 3) G allele acted as a risk factor in the endemic region but a protective factor in the non-endemic region.
Conclusions:
- Genetic variations in ICAM1, PECAM1, and CD36 significantly impact falciparum malaria manifestation in India.
- The PECAM1 exon 3 SNP demonstrates differential association with malaria risk depending on the endemicity of the region.
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