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

Lourembam, Sonia D.; Sawian, Clara E.; Baruah, Satyabrat Malla Bujar

doi:10.1016/j.meegid.2011.08.017

Cited by 11 publications

(12 citation statements)

References 27 publications

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“…Contrasting association of KIR3DL1 and KIR3DS1 with DF could be due to the fact that both segregate as alleles of a single locus. KIR3DL1 gene has been shown to be associated with susceptibility to tuberculosis and malaria in Indian populations (Lourembam et al, 2011;Pydi et al, 2013). KIR3DL1 is an inhibitory receptor, and binding to its ligand HLA-Bw4 may inhibit the activity of NK cells and might favour increased viral replication during the earlier stages of infection, leading to symptomatic disease.…”

Section: Discussionmentioning

confidence: 99%

Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India

Alagarasu

Bachal

Shah

et al. 2015

Int J Immunogenetics

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Killer cell immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells (NKs). Qualitative and quantitative differences in the type and the number of KIRs expressed on NK cells affect its activation which would influence the outcome of the disease. In this study, 114 hospitalized cases of dengue [82 dengue fever (DF) and 32 dengue haemorrhagic fever (DHF) cases] and 104 healthy controls (HC) without no known history of hospitalization for dengue-like illness were investigated for their KIR gene profile to find out the association of KIR genes with dengue disease severity. KIR gene profile was investigated using duplex sequence-specific priming polymerase chain reaction-based typing system. The results revealed a higher frequency of KIR3DL1 gene [P = 0.0225; odds ratio (OR) 4.1 95% confidence interval (CI) 1.1-14.8] and lower frequency of KIR3DS1/3DS1 genotype [P = 0.0225; OR 0.24 95% CI (0.068-0.88)] in DF cases compared to HC. Immunoglobulin-like receptor gene frequencies were not different between DHF and DF or HC. The results suggest that KIR3DL1/KIR3DS1 locus might be associated with the risk of developing DF.

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Section: Discussionmentioning

confidence: 99%

Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India

Alagarasu

Bachal

Shah

et al. 2015

Int J Immunogenetics

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“…Previous studies have reported a possible association of the predominance of activating KIR genes with susceptibility to malaria infections . It has been suggested that the predominance of activating genes (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have demonstrated the important influence of KIR and HLA ligand genes on the susceptibility to and outcomes of various noninfectious and infectious diseases , including malaria . Malaria infection has a variable clinical phenotype, ranging from mild febrile illness to severe disease and death, but infection can also occur in the absence of clinical symptoms.…”

Section: Introductionmentioning

confidence: 99%

“…The first study found that NK cell interferon (IFN)‐gamma production in response to Plasmodium falciparum antigens is, in part, regulated by KIR genes . Subsequently, the associations of KIR and HLA ligand genes with the susceptibility to and outcome of malaria infection have been found in studies conducted in different malaria‐exposed populations from Gambia, Kenya, Thailand, India and the Solomon Islands . However, no KIR genes associated with malaria in Brazilian endemic areas have been identified.…”

Section: Introductionmentioning

confidence: 99%

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Killer cell immunoglobulin‐like receptor (KIR) gene diversity in a population naturally exposed to malaria in Porto Velho, Northern Brazil

et al. 2015

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Killer cell immunoglobulin-like receptors (KIR) are expressed mainly in natural killer cells and specifically recognize human leukocyte antigen (HLA) class I molecules. The repertoire of KIR genes and KIR-HLA pairs is known to play a key role in the susceptibilities to and the outcomes of several diseases, including malaria. The aim of this study was to investigate the distribution of KIR genes, KIR genotypes and KIR-HLA pair combinations in a population naturally exposed to malaria from Brazilian Amazon. All 16 KIR genes investigated were present in the studied population. Overall, 46 KIR genotypes were defined. The two most common genotypes in the Porto Velho communities, genotypes 1 and 2, were present at similar frequencies as in the Americas. Principal component analysis based on the frequencies of the KIR genes placed the Porto Velho population closer to the Venezuela Mestizos, USA California hispanic and Brazil Paraná Mixed in terms of KIR gene frequencies. This analysis highlights the multi-ethnic profile of the Porto Velho population. Most of the individuals were found to have at least one inhibitory KIR-HLA pair. Seventy-five KIR-HLA pair combinations were identified. The KIR-2DL2/3_HLA-C1, KIR3DL1_HLA-Bw4 and KIR2DL1_HLA-C2 pairs were the most common. There was no association between KIR genes, KIR genotypes or KIR-HLA pair combinations and malaria susceptibility in the studied population. This is the first report on the distribution of KIR and known HLA ligands in the Porto Velho population. Taken together, these results should provide baseline information that will be relevant to population evolutionary history, malaria and other diseases studies in populations of the Brazilian Amazon.

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“…However, a recent GWAS analysis of 17,000 individuals estimated that known variants account for only 11% of the total genetic influence on malaria susceptibility (8). Notably, most studies of host genetic susceptibility to malaria, including the GWAS study noted above, have involved comparison of severe malaria cases to controls with non-severe (but symptomatic) malaria (9,10). This analytic framework could overlook genes that influence protection at the earlier pre-erythrocytic stages of the Pf life cycle, before blood stage infection is established.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory KIR ligands are associated with higherP. falciparumparasite prevalence

Digitale

Callaway

Martin

et al. 2020

Preprint

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Killer cell immunoglobulin-like receptors (KIR) and their HLA ligands influence the outcome of many infectious diseases. Data from a longitudinal cohort comprised of three study sites in Uganda with varying malaria transmission intensity show that presence of the HLA-C2 and HLA-Bw4 ligands for inhibitory KIR2DL1 and KIR3DL1, respectively, increase the likelihood of Plasmodium falciparum (Pf) parasitemia in an additive manner. For KIR2DL1/2/3, parasite prevalence was highest among individuals with KIR/HLA-C ligand pairs that are capable of the greatest cellular inhibition. Individuals homozygous for HLA-C2, which mediates strong inhibition via the near ubiquitous KIR2DL1 receptor, had the highest odds of parasitemia, while HLAC1/C2 heterozygotes had intermediate odds, and individuals homozygous for HLA-C1, which mediates weaker inhibition through KIR2DL2/3, had the lowest odds of parasitemia. A higher risk of parasitemia was also observed in the pairing of HLA-C1 with its receptor KIR2DL2 compared to its less inhibitory receptor KIR2DL3. Additionally, higher surface expression of HLA-C, the ligand for KIR2DL1/2/3, was associated with a higher likelihood of parasitemia. Together these data indicate that stronger KIR-mediated inhibition confers a higher risk of Pf parasitemia and suggest that KIR-expressing effector cells play a role in mediating anti-parasite immunity.

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

Cited by 11 publications

References 27 publications

Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India

Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India

Killer cell immunoglobulin‐like receptor (KIR) gene diversity in a population naturally exposed to malaria in Porto Velho, Northern Brazil

Inhibitory KIR ligands are associated with higherP. falciparumparasite prevalence

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