Dong Wenjia, Yu Junjie, Xu Siqi, Li Hongsheng
Department of Clinical Laboratory, The Second Hospital of Jiaxing, Zhejiang, China.
Front Genet. 2025 Sep 5;16:1543963. doi: 10.3389/fgene.2025.1543963. eCollection 2025.
Mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) plays a critical role in the metabolism of ethanol and nitroglycerin. Mutations in ALDH2 reduce enzymatic activity, impairing nitroglycerin metabolism. ALDH2 genetic polymorphisms exhibit significant regional variations across China. This study investigates the distribution of ALDH2 allelic and genotypic frequencies in patients with angina pectoris across northern (Luoyang, Henan), eastern (Jiaxing, Zhejiang), and southern (Guilin, Guangxi) China, and explores the relationship between ALDH2 genotypes and selected clinical characteristics.
A total of 1,084 angina pectoris patients were recruited from the three aforementioned regions. ALDH2 genotyping was performed using fluorescence quantitative PCR, and associations between genotypes and clinical characteristics, such as smoking and alcohol consumption histories, were analyzed.
The geographical distribution of the ALDH2 rs671 G→A mutation showed a significant increase in mutation frequency from northern to southern China. Genotypic distributions differed significantly across regions, with GG being predominant in northern China and higher frequencies of GA and AA observed in southern regions. Additionally, lifestyle factors such as smoking and alcohol consumption were significantly associated with the presence of the A allele, reflecting the interplay between genetics and environmental influences.
This study reveals significant regional differences in ALDH2 rs671 polymorphism and its association with lifestyle factors in angina pectoris patients across China. Since the ALDH2*2 variant markedly reduces the metabolic activation of nitroglycerin, these findings have important clinical implications: in regions with a higher prevalence of the A allele, patients may exhibit reduced therapeutic response to nitroglycerin. This highlights the need for region-specific and genotype-informed strategies in the management of angina pectoris.
线粒体乙醛脱氢酶2（ALDH2）在乙醇和硝酸甘油的代谢中起关键作用。ALDH2突变会降低酶活性，损害硝酸甘油的代谢。ALDH2基因多态性在中国各地呈现出显著的区域差异。本研究调查了中国北方（河南洛阳）、东部（浙江嘉兴）和南方（广西桂林）心绞痛患者中ALDH2等位基因和基因型频率的分布，并探讨了ALDH2基因型与所选临床特征之间的关系。
从上述三个地区招募了总共1084名心绞痛患者。使用荧光定量PCR进行ALDH2基因分型，并分析基因型与吸烟和饮酒史等临床特征之间的关联。
ALDH2 rs671 G→A突变的地理分布显示，从中国北方到南方，突变频率显著增加。基因型分布在各地区之间存在显著差异，GG基因型在中国北方占主导地位，而在南方地区观察到较高频率的GA和AA基因型。此外，吸烟和饮酒等生活方式因素与A等位基因的存在显著相关，反映了遗传和环境影响之间的相互作用。
本研究揭示了中国心绞痛患者中ALDH2 rs671多态性的显著区域差异及其与生活方式因素的关联。由于ALDH2*2变体显著降低了硝酸甘油的代谢活化，这些发现具有重要的临床意义：在A等位基因患病率较高的地区，患者可能对硝酸甘油的治疗反应降低。这突出了在心绞痛管理中采用区域特异性和基因型指导策略的必要性。
