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

Hiromi Saito; Atsuhiro Hirayama; Takeji Umemura; Satoru Joshita; Kenji Mukawa; Tomoaki Suga; Eiji Tanaka; Masao Ota

doi:10.1371/journal.pone.0195778

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

PLoS One. 2018 Apr 12;13(4):e0195778. doi: 10.1371/journal.pone.0195778. eCollection 2018.

Authors

Hiromi Saito¹, Atsuhiro Hirayama¹, Takeji Umemura¹, Satoru Joshita¹, Kenji Mukawa², Tomoaki Suga¹, Eiji Tanaka¹, Masao Ota¹

Affiliations

¹ Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
² Department of Gastroenterology, Suwa Red Cross Hospital, Suwa, Japan.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Case-Control Studies
Colitis, Ulcerative / epidemiology*
Colitis, Ulcerative / genetics*
Crohn Disease / epidemiology*
Crohn Disease / genetics*
Female
Gene Frequency
Genetic Predisposition to Disease*
Genotype
HLA Antigens / genetics*
Humans
Japan / epidemiology
Male
Receptors, KIR / genetics*

Substances

HLA Antigens
Receptors, KIR

Grants and funding

This research was supported in a part by a research grant from the Japan Society for the Promotion of Science KAKENHI (17K09416) (TU). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.