Umemura Takeji, Fujinaga Yasunari, Ashihara Norihiro, Ozawa Makiko, Kuraishi Yasuhiro, Watanabe Takayuki, Hamano Hideaki, Meguro Akira, Kawa Shigeyuki, Ota Masao
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.
Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan.
Gene. 2022 Apr 30;820:146212. doi: 10.1016/j.gene.2022.146212. Epub 2022 Feb 7.
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.
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.
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).
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.
IgG4相关性疾病（IgG4-RD）是一种免疫介导的疾病，其特征为血清IgG4浓度升高以及受累器官中有携带IgG4的浆细胞浸润。IgG4相关性主动脉周炎/动脉周炎是IgG4-RD中最近发现的一种影响心血管系统的疾病实体。由于与疾病发病相关的遗传因素尚不清楚，我们研究了与IgG4相关性主动脉周炎/动脉周炎易感性的遗传关联。
小规模全基因组关联分析发现，白细胞介素1受体1型（IL1R1）基因变异与75例IgG4-RD患者的IgG4相关性主动脉周炎/动脉周炎的发生相关。因此，在124例IgG4-RD患者（43例有主动脉周炎/动脉周炎，81例无主动脉周炎/动脉周炎）和344名健康受试者中选择了IL1R1基因中的8个单核苷酸多态性（SNP）并进行基因分型。
与无主动脉周炎/动脉周炎的患者相比，IgG4相关性主动脉周炎/动脉周炎患者中6个SNP（rs2287049、rs3917273、rs2160227、rs951192、rs3917318、rs7582198）的次要等位基因频率显著增加（校正P<0.05）。此外，由5个SNP（rs3917273、rs2160227、rs951192、rs3917318、rs7582198）组成的AGAAA单倍型在有主动脉周炎/动脉周炎的患者中频率显著更高（OR=2.41，95%CI：1.42-4.10）。
我们的研究结果表明，IL1R1基因多态性与IgG4相关性主动脉周炎/动脉周炎有关，并且某些遗传因素有可能影响特定IgG4-RD表现的风险。
