IL1R1 gene variants associate with disease susceptibility to IgG4-related periaortitis/periarteritis in IgG4-related disease

Takeji Umemura; Yasunari Fujinaga; Norihiro Ashihara; Makiko Ozawa; Yasuhiro Kuraishi; Takayuki Watanabe; Hideaki Hamano; Akira Meguro; Shigeyuki Kawa; Masao Ota

doi:10.1016/j.gene.2022.146212

IL1R1 gene variants associate with disease susceptibility to IgG4-related periaortitis/periarteritis in IgG4-related disease

Gene. 2022 Apr 30:820:146212. doi: 10.1016/j.gene.2022.146212. Epub 2022 Feb 7.

Authors

Affiliations

¹ Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan; Department of Life Innovation, Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan. Electronic address: tumemura@shinshu-u.ac.jp.
² Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: fujinaga@shinshu-u.ac.jp.
³ Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: 17MH001E@shinshu-u.ac.jp.
⁴ Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: makitano@shinshu-u.ac.jp.
⁵ Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: yasuhiro@shinshu-u.ac.jp.
⁶ Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: wat1400@shinshu-u.ac.jp.
⁷ Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan; Medical Informatics Division, Shinshu University Hospital, Matsumoto, Japan. Electronic address: hamano-hideaki@pref-nagano-hosp.jp.
⁸ Department of Ophthalmology and Visual Science, Yokohama City University School of Medicine, Yokohama, Japan. Electronic address: akmeguro@yokohama-cu.ac.jp.
⁹ Department of Internal Medicine, Matsumoto Dental University, Shiojiri, Japan. Electronic address: shigeyuki.kawa@mdu.ac.jp.
¹⁰ Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: otamasao@shinshu-u.ac.jp.

PMID: 35143941
DOI: 10.1016/j.gene.2022.146212

Abstract

Background: IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by high serum IgG4 concentration and IgG4-bearing plasma cell infiltration in affected organs. IgG4-related periaortitis/periarteritis is a recently identified disease entity in IgG4-RD that affects the cardiovascular system. Since the genetic factors related to disease onset are unclear, we examined the genetic associations with IgG4-related periaortitis/periarteritis susceptibility.

Methods: A small scale of genome-wide association analysis identified that interleukin 1 receptor type 1 (IL1R1) gene variants were correlated with the development of IgG4-related periaortitis/periarteritis in 75 patients with IgG4-RD. Accordingly, 8 single nucleotide polymorphisms (SNPs) in the IL1R1 gene were selected and genotyped in 124 patients with IgG4-RD (43 with periaortitis/periarteritis and 81 without periaortitis/periarteritis) and 344 healthy subjects.

Results: The minor allele frequencies of 6 SNPs (rs2287049, rs3917273, rs2160227, rs951192, rs3917318, rs7582198) were significantly increased in IgG4-related periaortitis/periarteritis patients compared with those without periaortitis/periarteritis (corrected P < 0.05). In addition, the frequency of the AGAAA haplotype, comprised of 5 SNPs (rs3917273, rs2160227, rs951192, rs3917318, rs7582198), was significantly higher in patients with periaortitis/periarteritis (OR = 2.41, 95% CI:1.42-4.10).

Conclusion: Our findings indicated that IL1R1 genetic polymorphisms contributed to IgG4-related periaortitis/periarteritis and the possibility of certain genetic factors influencing the risk of specific IgG4-RD manifestations.

Keywords: IL1R1; IgG4-related disease; IgG4-related periaortitis/periarteritis; SNP.

MeSH terms

Adult
Aged
Aged, 80 and over
Arteritis / genetics*
Disease Susceptibility
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Immunoglobulin G / blood
Immunoglobulin G4-Related Disease / genetics*
Inflammation
Male
Middle Aged
Polymorphism, Single Nucleotide*
Receptors, Interleukin-1 Type I / genetics*
Retroperitoneal Fibrosis / genetics*

Substances

IL1R1 protein, human
Immunoglobulin G
Receptors, Interleukin-1 Type I