Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4.
Genome-wide scans have detected linkage to celiac disease (CD) in several genomic locations, including 19q13.4. Killer immunoglobulin-like receptor (KIR) genes map to the region and encode receptors of natural killer (NK) cells and certain T cells that modulate cytolitic activity through interactions with HLA class I ligands, participating in the innate immune response. We performed KIR genotyping in a group of 70 CD patients of Basque origin and compared gene content, genotype and haplotype frequencies to ethnically matched blood-donors. The frequency of gene combination KIR2DL5B(+)/KIR2DL5A(-) was significantly higher in the disease group, and this result was confirmed in a second group of 343 CD patients and 160 controls of Spanish origin, suggesting an implication of this 'unexpressed' gene with increased susceptibility to CD (combined OR of 3.63 (95% CI: 1.76-7.51; P=0.0004)), possibly due to the lack of an efficient inhibitory signal. Our results support the role of the KIR gene cluster in celiac disease and replicate the CD-susceptibility locus at 19q13.4.
Santin
I
I
Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, Bizkaia, Spain.
Castellanos-Rubio
A
A
Perez de Nanclares
G
G
Vitoria
J C
JC
Castaño
L
L
Bilbao
J R
JR
D002446:Celiac Disease / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D011971:Receptors, Immunologic / Q000235:genetics*; D054340:Receptors, KIR; D054346:Receptors, KIR2DL5; D013030:Spain
C515080:KIR2DL5A protein, human; C515081:KIR2DL5B protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054346:Receptors, KIR2DL5