Killer-Cell Immunoglobulin-like Receptor Diversity in an Admixed South American Population

Abstract

Natural Killer (NK) cells are innate immune cells that mediate antiviral and antitumor responses. NK cell activation and induction of effector functions are tightly regulated by the integration of activating and inhibitory receptors such as killer immunoglobulin-like receptors (KIR). KIR genes are characterized by a high degree of diversity due to presence or absence, gene copy number and allelic polymorphism. The aim of this study was to establish the distribution of KIR genes and genotypes, to infer the most common haplotypes in an admixed Colombian population and to compare these KIR gene frequencies with some Central and South American populations and worldwide. A total of 161 individuals from Medellin, Colombia were included in the study. Genomic DNA was used for KIR and HLA genotyping. We analyzed only KIR gene-content (presence or absence) based on PCR-SSO. The KIR genotype, most common haplotypes and combinations of KIR and HLA ligands frequencies were estimated according to the presence or absence of KIR and HLA genes. Dendrograms, principal component (PC) analysis and Heatmap analysis based on genetic distance were constructed to compare KIR gene frequencies among Central and South American, worldwide and Amerindian populations. The 16 KIR genes analyzed were distributed in 37 different genotypes and the 7 most frequent KIR inferred haplotypes. Importantly, we found three new genotypes not previously reported in any other ethnic group. Our genetic distance, PC and Heatmap analysis revealed marked differences in the distribution of KIR gene frequencies in the Medellin population compared to worldwide populations. These differences occurred mainly in the activating KIR isoforms, which are more frequent in our population, particularly KIR3DS1. Finally, we observed unique structural patterns of genotypes, which evidences the potential diversity and variability of this gene family in our population, and the need for exhaustive genetic studies to expand our understanding of the KIR gene complex in Colombian populations.

Unveiling the Significance of HLA and KIR Diversity in Underrepresented Populations

“…Consistent with the findings of previous studies, HLA-C was the most common ligand, along with HLA-Bw4, with an approximate frequency of 85%. The researchers also observed a low prevalence of KIR haplotype A, constituting only 13% of the population, aligning with findings in other Central and South American populations [ 55 ]. In another study involving a Brazilian cohort [ 45 ], researchers observed KIR frequencies exceeding 90% for KIR2DL1 , KIR2DL3 , KIR3DL1 (inhibitory KIR), KIR3DS1 (activating KIR), and KIR2PD1 (pseudogene).…”

“…In a mixed Colombian population of European (75%), African (7%), and Native American (18%) descent, characterization of KIRs based on polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) revealed KIR2DP1 and KIR2DL1 to be most prevalent, accounting for 77% of the population [ 55 ]. Consistent with the findings of previous studies, HLA-C was the most common ligand, along with HLA-Bw4, with an approximate frequency of 85%.…”

KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection

“…However, further validation of this observation in an independent cohort with various HCV-genotypes is recommended. The KIR diversity between different populations reported by other groups [13,14] is not a likely explanation as there was no statistically significant difference between the frequency of KIR allelotype in the non-cancer HCV patients in the Italian cohort and the Egyptian cohort (25.6% vs. 27%, p = 0.8843).…”

Killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands in a Brazilian population

“…The discoveries about KIR polymorphism, KIR gene content, and copy number/KIR allelic variation have guided the research into the impact of KIR genetic variation on human health. [13][14][15] Due to its high level of diversity, the Brazilian population represents a unique group for research purposes. Thus, the main aim of this research was to investigate the presence of KIR genes in Brazil, and draw comparisons with other populations.…”