Author:
Yamaguchi Naoyuki,Sakaguchi Takuki,Isomoto Hajime,Inamine Tatsuo,Tsukamoto Ryoya,Fukuda Daisuke,Ohnita Ken,Kanda Tsutomu,Matsushima Kayoko,Hirayama Tatsuro,Yashima Kazuo,Tsukamoto Kazuhiro
Abstract
Abstract
Background
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.
Results
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.
Conclusion
LRP1 and CAPZA1 polymorphisms may be associated with the development of GMA.
Funder
a research grant from the Non-Profit Organization Aimed to Support Community Medicine Research in Nagasaki
Publisher
Springer Science and Business Media LLC
Subject
Environmental Science (miscellaneous),Genetics,Social Psychology
Cited by
2 articles.
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