Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India.
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.


CONCLUSIONS
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.
Sinha
Swapnil
S
Division of Molecular and Structural Biology, Central Drug Research Institute, Post box 173, Chattar Manzil, Mahatma Gandhi Marg, Lucknow-226001, India. swaps.gene@gmail.com
Qidwai
Tabish
T
Kanchan
Kanika
K
Anand
Prerna
P
Jha
Ganga N
GN
Pati
Sudhanshu S
SS
Mohanty
Sanjib
S
Mishra
Saroj K
SK
Tyagi
Prajesh K
PK
Sharma
Surya K
SK
Venkatesh
Vimala
V
Habib
Saman
S
D000483:Alleles; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006790:Host-Parasite Interactions; D006801:Humans; D007194:India / Q000453:epidemiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics*; D010963:Plasmodium falciparum / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D018955:CD36 Antigens; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1