Yamaguchi Naoyuki, Sakaguchi Takuki, Isomoto Hajime, Inamine Tatsuo, Tsukamoto Ryoya, Fukuda Daisuke, Ohnita Ken, Kanda Tsutomu, Matsushima Kayoko, Hirayama Tatsuro, Yashima Kazuo, Tsukamoto Kazuhiro
Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, 683-8504, Japan.
Genes Environ. 2023 May 17;45(1):18. doi: 10.1186/s41021-023-00274-5.
Helicobacter pylori secretes cytotoxin-associated gene A (CagA) into the gastric epithelium, causing gastric mucosal atrophy (GMA) and gastric cancer. In contrast, host cells degrade CagA via autophagy. However, the association between polymorphisms in autophagy-related genes and GMA must be fully elucidated.
We evaluated the association between single nucleotide polymorphisms (SNPs) in autophagy-related genes (low-density lipoprotein receptor-related protein 1, LRP1; capping actin protein of muscle Z-line alpha subunit 1, CAPAZ1; and lysosomal-associated membrane protein 1, LAMP1) and GMA in 200 H. pylori-positive individuals. The frequency of the T/T genotype at rs1800137 in LRP1 was significantly lower in the GMA group than in the non-GMA group (p = 0.018, odds ratio [OR] = 0.188). The frequencies of the G/A or A/A genotype at rs4423118 and T/A or A/A genotype at rs58618380 of CAPAZ1 in the GMA group were significantly higher than those in the non-GMA group (p = 0.029 and p = 0.027, respectively). Multivariate analysis revealed that C/C or C/T genotype at rs1800137, T/A or A/A genotype at rs58618380, and age were independent risk factors for GMA (p = 0.038, p = 0.023, and p = 0.006, respectively). Furthermore, individuals with the rs1800137 C/C or C/T genotype of LRP1 had a 5.3-fold higher susceptibility to GMA. These genetic tests may provide future directions for precision medicine for individuals more likely to develop GMA.
LRP1 and CAPZA1 polymorphisms may be associated with the development of GMA.
幽门螺杆菌将细胞毒素相关基因A（CagA）分泌到胃上皮细胞中，导致胃黏膜萎缩（GMA）和胃癌。相比之下，宿主细胞通过自噬降解CagA。然而，自噬相关基因多态性与GMA之间的关联仍有待充分阐明。
我们评估了200例幽门螺杆菌阳性个体中自噬相关基因（低密度脂蛋白受体相关蛋白1，LRP1；肌动蛋白帽蛋白Z线α亚基1，CAPAZ1；溶酶体相关膜蛋白1，LAMP1）的单核苷酸多态性（SNP）与GMA之间的关联。LRP1基因rs1800137位点T/T基因型在GMA组中的频率显著低于非GMA组（p = 0.018，比值比[OR]=0.188）。CAPAZ1基因rs4423118位点G/A或A/A基因型以及rs58618380位点T/A或A/A基因型在GMA组中的频率显著高于非GMA组（分别为p = 0.029和p = 0.027）。多因素分析显示，rs1800137位点C/C或C/T基因型、rs58618380位点T/A或A/A基因型以及年龄是GMA的独立危险因素（分别为p = 0.038、p = 0.023和p = 0.006）。此外，携带LRP1基因rs1800137位点C/C或C/T基因型的个体发生GMA的易感性高5.3倍。这些基因检测可能为更易发生GMA的个体的精准医学提供未来方向。
LRP1和CAPZA1基因多态性可能与GMA的发生有关。
