Abstract

Volume.123 Number.11

A Review

Genetic Factors and Mechanism of the Onset of Behçet's Disease
Masaki Takeuchi
Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine

Behçet's disease (BD) is a systemic inflammatory disease characterized by repeated of relapsing episodes and remissions. Multiple genetic and environmental factors may be associated with the onset of BD. While several genome-wide association studies have identified susceptibility genes for BD, the understanding of genetic factors is still unclear. We conducted the largest genetic analysis study till date with an aim to further identify susceptibility genes and elucidate the pathology of BD. An international BD consortium was formed that involved research institutions from five nations to collect specimens from Japanese, Turkish, and Iranian individuals (3,477 patients and 3,342 healthy individuals). We then used Immunochip (Illumina, Inc.), a microarray with high-density single nucleotide polymorphism (SNP) arranged for immunogenetic gene locus, to implement genotyping. The present study identified genome-wide correlations that met a significant threshold of p<5×10-8 in six novel susceptibility loci (IL1A-IL1B, RIPK2, ADO-EGR2, LACC1, IRF8, and CEBPB-PTPN1). Many susceptibility genes identified in this study (IL1A, IL1B, LACC1, IRF8, and CEBPB) were associated with innate immunity, the body's biological defense mechanism against pathogens. Functional analysis revealed that the risk allele of rs4402765, the SNP of the loci IL1A-IL1B, were associated with both increased interleukin (IL)-1β and decreased IL-1α levels. Thus, abnormal biological defense against pathogens may be closely involved in the onset of BD. Moreover, risk factors for the onset of BD may include innate immune enhancement and the suppression of certain immune pathways.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 123: 1029-1037, 2019.

Key words
Susceptibility gene, Innate immunity, Behçet's disease, Genome-wide association study (GWAS), Single nucleotide polymorphism (SNP)
Reprint requests to
Masaki Takeuchi, M.D., Ph.D. Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine. 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan