Differential association of KIR gene loci to risk of malaria in ethnic groups of Assam, Northeast India

Abstract

Receptors encoded within the Natural Killer Cell (NKC) complex and Killer Immunoglobulin like (KIRs) genomic regions have been suggested to influence malaria pathogenesis and infection susceptibility. We have examined KIR locus in relation to risk of infection and disease in Tea tribes (TT) of Austro Asiatic affinity and Tibeto-Burman (TB) populations from malaria endemic regions of Assam. Consistent with differences in their genetic background, KIR gene loci frequencies differed in studied groups. Surprisingly, KIR3DS1 frequency in TT was low (17%) and comparable to that reported from African populations.KIR3DL1 frequency was positively associated with malaria severity (Pearson phi, R2=0.297 p=0.006) and logistic regression modelling predicted KIR3DL1 as a risk factor in complicated malaria [Odds Ratio (95% C.I)]=[6.39 (1.34–30.60)]. An interaction between ethnicity and KIR3DL1 was also seen where higher proportion of KIR3DL1 positive and complicated malaria patients belonged to Tea tribes (p=0.009). Notably, four activating genes protected from frequent malaria (p=0.02) while six activating genes enhanced the risk of complicated malaria (p=0.05). Combination of KIR2DS4, KIR2DS4del, KIR2DS5 negatively influenced disease outcome in Tea tribes (p=0.048) but not in Tibeto-Burman.In conclusion our data indicates KIR gene loci differentially influenced malaria outcome in Tea tribes and Tibeto-Burman and that four activating genes appeared to provide optimal activation that protected from frequent episodes of malaria. Our data also indicated KIR3DS1 to be an ancestral genotype, maintained at low frequency possibly by malaria in the Austro Asiatic tribes.