Nephrolithiasis is a common urological disorder and has become a significant global public health issue. Aldehyde dehydrogenase 2 (ALDH2), an important endogenous antioxidant enzyme involved in alcohol metabolism, has been shown to exert protective effects in various diseases. However, the specific role of ALDH2 gene polymorphisms in kidney stone formation, particularly in relation to alcohol consumption, remains poorly understood.
In this study, 979 nephrolithiasis patients and 1,009 healthy controls, matched for sex, age, and ethnicity, were enrolled. Genotyping of single nucleotide polymorphisms (SNPs) was performed, and a nephrolithiasis mouse model with Aldh2 deficiency was established to assess the susceptibility to kidney stone formation under Aldh2-deficient conditions.
The ALDH2 rs671 polymorphism and three nearby SNPs (rs3782886, rs4766566, and rs2188380) were significantly associated with nephrolithiasis. Moreover, in the ethylene glycol (EG)-induced nephrolithiasis model, pathological examination of kidney sections from Aldh2 knockout mice exposed to alcohol revealed a significantly higher calcium oxalate crystal deposition score, accompanied by elevated levels of 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA), compared with that in wild-type mice.
ALDH2 deficiency was significantly associated with an increased risk of nephrolithiasis, and this risk was further exacerbated by alcohol consumption. These findings enhance our understanding of the role of ALDH2 in kidney stone pathogenesis and may inform the development of novel strategies for the prevention and treatment of nephrolithiasis.
Molecular genetics & genomic medicine. 2026 Jan [Epub]
Tao Liu, Yu-Qi Lv, Xiao-Liang Huang, Yuan-Liang Xie, Yu Ye, Yang Chen, Chao Feng, Qiu-Yan Wang, Zeng-Nan Mo, Ming Liao, Tian-Yu Li, Jun Liao
Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China., Department of Urology, The Sixth People's Hospital of Nanning, Nanning, Guangxi, China., Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Tumor Hospital of Guangxi Medical University, Nanning, China., Department of Urology, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China., Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China., Center for Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China., Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.