Genetic variants killer cell receptors may contribute to PSC

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J Hepatol. 2007 May

Particular genetic variants of ligands for natural killer cell

receptors may contribute to the HLA associated risk of primary

sclerosing cholangitis.

Karlsen TH, Boberg KM, Olsson M, Sun JY, Senitzer D, Bergquist A,

Schrumpf E, Thorsby E, Lie BA.

Medical Department, Rikshospitalet-Radiumhospitalet Medical

Center, University of Oslo,

BACKGROUND/AIMS: Combinations of killer immunoglobulin-like

receptors (KIRs) and HLA class I ligands that reduce natural killer

(NK) cell inhibition have been shown to increase risk for autoimmune

diseases. We aimed to clarify to what extent such combinations

influence susceptibility to primary sclerosing cholangitis (PSC).

METHODS: Three hundred and sixty-five Scandinavian PSC patients and

368 healthy controls were genotyped for the presence or absence of

genes encoding all KIRs using a PCR-SSP approach. KIR binding site

variation of HLA-A, -B and -C was also determined. RESULTS: The KIR

gene frequencies were similar among patients and controls. However,

the frequency of HLA-Bw4 and -C2, which are ligands for the inhibitory

KIRs 3DL1 and 2DL1, respectively, was significantly reduced in PSC

patients as compared with controls (38.2% vs. 54.7%,

P(corrected)[P©]=0.0006 and 42.7% vs. 56.9%, P©=0.009,

respectively). Two HLA risk haplotypes in PSC (carrying DRB1*0301 or

DRB1*1501, respectively) were devoid of both of these alleles, and

carried the 5.1 variant of the major histocompatibility complex class

I chain-related A (MICA) gene previously reported to influence PSC

susceptibility. CONCLUSIONS: Particular variants of ligands for NK

cell receptors encoded at three neighbouring genes in the HLA complex

may contribute to PSC associations observed in this genetic region.

PMID: 17383044 [PubMed - indexed for MEDLINE]