Faculty Collaboration Database

Susceptibility to Crohn's disease is mediated by KIR2DL2/KIR2DL3 heterozygosity and the HLA-C ligand. Immunogenetics 2009 Oct;61(10):663-71

Date

10/01/2009

Pubmed ID

19789864

Pubmed Central ID

PMC2813946

DOI

10.1007/s00251-009-0396-5

Scopus ID

2-s2.0-70350542586 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

In the present study, we investigated the relationship between the KIR loci and the genes encoding their HLA ligands and genetic susceptibility to Crohn's disease (CD). Analyses of the interactions between KIR3DL1, KIR2DL1, KIR2DL2, and KIR2DL3 with their respective HLA ligands indicate that there is a protective effect for KIR2DL2 in the absence of its HLA ligand C1. Given that KIR2DL2 and KIR2DL3 segregate as alleles, we compared their genotypic distributions to expectations under Hardy-Weinberg Equilibrium (HWE) with regard to the HLA ligand C1 status. While all the genotypic distributions conform to expectations under HWE in controls, in C2 ligand homozygous cases there is significant deviation from HWE, with a reduction of KIR2DL2, KIR2DL3 heterozygotes. KIR2DL2, KIR2DL3 heterozygosity is the only genotypic combination that confers protection from CD. In addition to the protective effect (OR = 0.44, CI = 0.22-0.87; p = 0.018) observed in C2 ligand homozygotes, the KIR2DL2, KIR2DL3 genotype is predisposing (OR = 1.34, CI = 1.03-4.53; p = 0.031) in the presence of C1 ligand. A test for trend of HLA class I C ligand group genotypes with KIR2DL2, KIR2DL3 heterozygosity in cases and controls indicates that C1, C2 ligand group heterozygotes have an intermediate effect on predisposition. These results show for the first time that disease susceptibility may be related to heterozygosity at a specific KIR locus, and that HLA ligand genotype influences the relative effect of the KIR genotype.

Author List

Hollenbach JA, Ladner MB, Saeteurn K, Taylor KD, Mei L, Haritunians T, McGovern DP, Erlich HA, Rotter JI, Trachtenberg EA

Author

Ling Mei MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Alleles
California
Case-Control Studies
Cohort Studies
Crohn Disease
Genetic Predisposition to Disease
Genotype
HLA-C Antigens
Heterozygote
Humans
Jews
Ligands
Polymorphism, Single Nucleotide
Receptors, KIR2DL2
Receptors, KIR2DL3
Single-Blind Method
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization