Evidence for genetic linkage between a polymorphism in the GNAS gene and malaria in South Indian population

Abstract

The complex imprinted GNAS locus which encodes G-alpha subunit (Gαs) is involved in a number of G-protein coupled signaling pathways in eukaryotic cells. Erythrocyte invasion by Plasmodium falciparum parasites is significantly regulated by protein of GNAS gene. This study was designed to evaluate the association between single nucleotide polymorphisms (SNPs) present in GNAS locus and susceptibility to malaria. In this case control study, individuals affected by P. falciparum malaria (n=230), Plasmodium vivax malaria (n=230) and normal controls (n=230) were tested for the association of eighteen (18) known SNPs to evaluate their role in the onset of the disease. There was no significant difference in genotype frequencies of all the SNPs tested between P. falciparum and P. vivax affected individuals. However, when Bonferroni correction for multiple comparisons were performed as a control, our results demonstrated alleles and genotypes of rs7121: C>T (NC_000020.10:g.57478807C>T), a silent polymorphism situated in the exon 5, were significantly (p<0.05) associated with susceptibility to malaria in the South Indians participants. Our results demonstrate that population specific polymorphisms that exist in GNAS gene may alter the risk of occurrence of malaria.

Keywords: ASW; Americans of African Ancestry in SW USA; CHD; CI; CNV; Chinese in Metropolitan Denver; EDTA; G-alpha subunit; G-protein coupled receptor; GNAS; GPCR; Genotype; Gαs; LWK; Luhya in Webuye, Kenya; MKK; Maasai in Kinyawa; Malaria; OR; PVM; Plasmodium; RFLP; SNP; South India; YRI; Yoruba in Ibadan; beta 2 adrenoreceptor; cAMP; confidence interval; copy number variation; cyclic adenosine monophosphate; ethylenediaminetetraacetic acid; odds ratios; parasitophorous vacuole membrane; restriction fragment length polymorphism; single nucleotide polymorphism; β2AR.