Association between KIR-HLA combination and ulcerative colitis and Crohn's disease in a Japanese population

• Published in: PloS one Vol. 13; no. 4; p. e0195778
• Main Authors: Saito, Hiromi, Hirayama, Atsuhiro, Umemura, Takeji, Joshita, Satoru, Mukawa, Kenji, Suga, Tomoaki, Tanaka, Eiji, Ota, Masao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12-04-2018; Public Library of Science (PLoS)
• Subjects: Alleles; Analysis; Biology and Life Sciences; Case-Control Studies; Colitis, Ulcerative - epidemiology; Colitis, Ulcerative - genetics; Crohn Disease - epidemiology; Crohn Disease - genetics; Crohn's disease; Crohns disease; Female; Gastroenterology; Gene Frequency; Genetic aspects; Genetic Predisposition to Disease; Genomes; Genotype; Genotype & phenotype; Glycoproteins; Haplotypes; Health aspects; Hepatitis; Hepatology; Histocompatibility antigen HLA; HLA Antigens - genetics; Human leukocyte antigen test; Humans; Immunity; Immunoglobulin-like receptors; Inflammatory bowel disease; Inflammatory bowel diseases; Innate immunity; Intestine; Japan - epidemiology; Japanese (Asian people); Killer cell immunoglobulin-like receptors; Ligands; Male; Medicine; Medicine and Health Sciences; Natural killer cells; Patients; People and Places; Population; Potassium channels (inwardly-rectifying); Receptors; Receptors, KIR - genetics; Ulcerative colitis; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0195778

Inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn's disease (CD). Natural killer cell responses play a crucial role in autoimmune disease through innate immunity, in which killer cell immunoglobulin-like receptors (KIRs) are closely involved. Although the genetic combination of KIRs with their specific HLA class I ligands has been associated with IBD in Caucasians, such KIR-HLA receptor-ligand combinations are not fully understood in the Japanese. We investigated 14 KIR genes along with HLA-Bw and -C ligands in 90 patients with UC and 50 patients with CD and compared them with the characteristics of 325 healthy control subjects. The frequency of HLA-Bw4 was significantly increased in patients with UC (P = 1.3 × 10-6; odds ratio [OR] = 3.39) and CD (P = 0.0065; OR = 2.32) versus controls. The UC group had a significantly higher frequency of KIR2DS3 (P = 0.024; OR = 1.94) and lower frequency of KIR2DS4 (P = 0.019; OR = 0.40) and KIR2DL1-HLA-C2 (P = 0.035; OR = 0.47). The Tel-A/B haplotype was significantly decreased in UC patients (P = 0.0056; OR = 0.49). The frequency of KIR3DL1-HLA-Bw4 was significantly higher in patients with UC (P = 4.3 × 10-6; OR = 3.12) and CD (P = 0.0067; OR = 2.30). In conclusion, HLA-Bw4 and KIR-HLA pairs may play an important role in the genetic susceptibility to IBD in the Japanese.