In contrast to other stimulatory natural killer cell immunoglobulin-like receptor loci, several KIR2DS5 alleles predominate in African Americans

Hou, Lihua; Chen, Minghua; Jiang, Bo; Kariyawasam, Kanthi; Ng, Jennifer; Hurley, Carolyn Katovich

doi:10.1016/j.humimm.2009.04.028

Cited by 15 publications

(15 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike Europeans, however, KIR2DS5 is polymorphic in Africans and African Americans. We found 10 alleles in Ugandans, consistent with previous reports from African Americans [the Immuno Polymorphism Database (IPD)], located in both cB and tB but most commonly found in those cB regions that also contain KIR2DP1 and KIR2DL1 (26,27). The dominant allele, KIR2DS5*005, is the only allele found in both cB and tB, and it is probably ancestral; when in either location, it was similar in frequency between cases and controls.…”

Section: Discussionsupporting

confidence: 89%

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

Nakimuli

Chazara²,

Hiby³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

135

146

View full text Add to dashboard Cite

In sub-Saharan Africans, maternal mortality is unacceptably high, with >400 deaths per 100,000 births compared with <10 deaths per 100,000 births in Europeans. One-third of the deaths are caused by pre-eclampsia, a syndrome arising from defective placentation. Controlling placentation are maternal natural killer (NK) cells that use killer-cell immunoglobulin-like receptor (KIR) to recognize the fetal HLA-C molecules on invading trophoblast. We analyzed genetic polymorphisms of maternal KIR and fetal HLA-C in 484 normal and 254 pre-eclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of maternal KIR AA genotypes and fetal HLA-C alleles encoding the C2 epitope associates with pre-eclampsia [P = 0.0318, odds ratio (OR) = 1.49]. The KIR genes associated with protection are located in centromeric KIR B regions that are unique to sub-Saharan African populations and contain the KIR2DS5 and KIR2DL1 genes (P = 0.0095, OR = 0.59). By contrast, telomeric KIR B genes protect Europeans against pre-eclampsia. Thus, different KIR B regions protect sub-Saharan Africans and Europeans from pre-eclampsia, whereas in both populations, the KIR AA genotype is a risk factor for the syndrome. These results emphasize the importance of undertaking genetic studies of pregnancy disorders in African populations with the potential to provide biological insights not available from studies restricted to European populations.Uganda | pre-eclampsia | NK cells | maternal mortality | KIR

show abstract

Section: Discussionsupporting

confidence: 89%

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

Nakimuli

Chazara²,

Hiby³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

135

146

View full text Add to dashboard Cite

show abstract

“…In general, there appears to be more alleles at each locus with lower frequencies in African Americans compared to European American or Asian populations. This diversity has also been observed for other KIR loci in this population (Hou et al 2009;Hou et al 2010). This increased diversity is also observed for loci other than KIR .…”

Section: Discussionsupporting

confidence: 82%

The characteristics of allelic polymorphism in killer-immunoglobulin-like receptor framework genes in African Americans

et al. 2011

Self Cite

View full text Add to dashboard Cite

The frequencies of alleles of killer cell immunoglobulin like receptor genes, KIR3DL3 and KIR3DL2, and the carrier frequency of KIR2DL4 alleles have been determined from a population of African Americans (n=100) by DNA sequencing of the coding regions. Fifty alleles of KIR3DL3 were observed with the most frequent, KIR3DL3*00901 (13%). KIR3DL2 was also diverse, 32 alleles with KIR3DL2*00103 the most frequent (17%). For KIR2DL4, of the 18 alleles observed, one allele, KIR2DL4*00103 was found in 64 of the 100 individuals. Thirty six novel alleles encoding a total of 28 unique receptors are described. Pairwise comparisons among all of the alleles at each locus suggest a predominance of synonymous substitutions. The variation at all three framework loci fits a neutral model of evolution.

show abstract

“…In exhibiting these distinctive differences between inhibitory and activating receptors, the Māori and Polynesians are similar to the other populations for which KIR alleles and haplotypes have been described at high resolution (Gendzekhadze et al 2009; Norman et al 2013; Vierra-Green et al 2012; Yawata et al 2006). The exception is KIR2DS5, which is polymorphic in sub-Saharan Africans (Hou et al 2009; Norman et al 2013). …”

Section: Resultsmentioning

confidence: 99%

KIR diversity in Māori and Polynesians: populations in which HLA-B is not a significant KIR ligand

et al. 2014

View full text Add to dashboard Cite

HLA class I molecules and killer cell immunoglobulin-like receptors (KIR) form a diverse system of ligands and receptors that individualize human immune systems in ways that improve the survival of individuals and populations. Human settlement of Oceania by island-hopping East and Southeast Asian migrants started ~3,500 years ago. Subsequently, New Zealand was reached ~750 years ago by ancestral Māori. To examine how this history impacted KIR and HLA diversity, and their functional interaction, we defined at high resolution the allelic and haplotype diversity of the 13 expressed KIR genes in 49 Māori and 34 Polynesians. Eighty KIR variants, including four ‘new’ alleles, were defined; as were 35 centromeric and 22 telomeric KIR region haplotypes, which combine to give >50 full-length KIR haplotypes. Two new and divergent variant KIR form part of a telomeric KIR haplotype, which appears derived from Papua New Guinea and was probably obtained by the Asian migrants en route to Polynesia. Māori and Polynesian KIR are very similar, but differ significantly from African, European, Japanese and Amerindian KIR. Māori and Polynesians have high KIR haplotype diversity with corresponding allotype diversity being maintained throughout the KIR locus. Within the population each individual has a unique combination of HLA class I and KIR. Characterizing Māori and Polynesians is a paucity of HLA-B allotypes recognized by KIR. Compensating for this deficiency are high frequencies (>50%) of HLA-A allotypes recognized by KIR. These HLA-A allotypes are ones that modern humans likely acquired from archaic humans at a much earlier time.

show abstract

In contrast to other stimulatory natural killer cell immunoglobulin-like receptor loci, several KIR2DS5 alleles predominate in African Americans

Cited by 15 publications

References 36 publications

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

The characteristics of allelic polymorphism in killer-immunoglobulin-like receptor framework genes in African Americans

KIR diversity in Māori and Polynesians: populations in which HLA-B is not a significant KIR ligand

Contact Info

Product

Resources

About