A deep look at KIR–HLA in Amerindians: Comprehensive meta-analysis reveals limited diversity of KIR haplotypes

Killer-cell immunoglobulin-like receptors (KIR) are highly polymorphic and have been associated to several diseases. Their ligands are specific human leukocyte antigens (HLA) molecules, expressed on the majority of cells. Only few genetically isolated populations have been characterized for the frequency of KIR–HLA combinations. The aim of this work was summarize and reanalyze the data described in recent publications regarding KIR and HLA in Amerindians. In total, 1258 individuals from 23 Amerindian populations were analyzed. All population samples were previously genotyped for KIR presence/absence polymorphism; KIR allelic content was poorly described. Only 9 of the 23 populations were genotyped for HLA class I. Based on the KIR gene-content profiles, we estimated the most common Amerindian KIR gene-content haplotypes, information never reported before for many of these populations. When the HLA genes started to be analyzed in many of these groups, KIR genes were still not well characterized. Therefore, they have never been analyzed in a joint context. We thoroughly examined the HLA haplotypes of these populations; for the first time, we are showing the frequencies of the known HLA ligands of most of these populations, which had been separately studied for both KIR and HLA. Amerindians exhibits a low diversity of KIR gene-content haplotypes when compared to most worldwide population. We compared the KIR–HLA diversity within and between Amerindian groups trying to understand the natural causes of variation. This study corroborates the hypothesis that demographic factors such as founder effect played a major role in shaping KIR diversity in Amerindians and may contribute to understand the importance of KIR–HLA for human health and disease.