Min Xue, Zhou Yu-Lan, Qu Yun-Fei, Liao Zhao-Fu, Li Heng, Cheng Jie, Liang Li-Li, Mo Hai-Liang, Wu Zhu-Guo, Xiong Xing-Dong
Dongguan Key Laboratory of Aging and Anti-Aging, Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Cardiovascular Center, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523808, P.R. China.
Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, P.R. China.
Lipids Health Dis. 2025 Jan 2;24(1):1. doi: 10.1186/s12944-024-02417-1.
The fat mass and obesity-associated protein (FTO) has been showed to be involved in the pathogenesis and progression of coronary artery disease (CAD). However, the effects of FTO variants on CAD risk remain poorly understood. We herein genotyped three SNPs (rs1121980, rs72803657, and rs4783818) in FTO to investigate the influence of FTO polymorphisms on individual susceptibility to CAD.
Genotyping for the three SNPs (rs1121980, rs72803657, and rs4783818) was conducted in a cohort of 712 CAD cases with 349 myocardial infarction (MI) cases and 701 control participants, utilizing the polymerase chain reaction-ligation detection reaction (PCR-LDR) technique. The associations of these SNPs with CAD were analyzed using multivariate logistic regression, and the associations with lipid profiles were assessed by the Kruskal-Wallis or Wilcoxon-Mann-Whitney tests.
The A allele (OR = 1.26, 95% CI = 1.01-1.57, and P = 0.044) and the AA genotype (OR = 3.13, 95% CI = 1.53-6.38, and P = 0.002) of FTO rs1121980 were significantly associated with an elevated risk of CAD. Similarly, the A allele (OR = 1.54, 95% CI = 1.18-2.02, and P = 0.002) and the AA genotype (OR = 5.61, 95% CI = 2.57-12.27, and P < 0.001) of rs1121980 exhibited increased MI risk. This SNP also showed significant associations under recessive genetic models for both CAD and MI (OR = 3.09, 95% CI = 1.52-6.27, P = 0.002 for CAD; OR = 5.40, 95% CI = 2.49-11.71, P < 0.001 for MI). However, the other two SNPs did not show significant associations with CAD or MI risks under any genetic model tested. Stratified analyses indicated a more pronounced association of the A allele with increased CAD/MI risk among younger participants, non-smokers, and non-drinkers. Interestingly, A allele carriers in younger subjects exhibited higher triglyceride (TG) levels and lower high-density lipoprotein cholesterol (HDL-C) levels compared to non-carriers (P < 0.05).
Our data provides the first evidence that the FTO rs1121980 polymorphism is associated with an increased risk of CAD in the Chinese population. This association is more significant in younger subjects, likely due to the elevated TG levels and reduced HDL-C levels.
脂肪量和肥胖相关蛋白（FTO）已被证明参与冠状动脉疾病（CAD）的发病机制和进展。然而，FTO变异对CAD风险的影响仍知之甚少。我们在此对FTO中的三个单核苷酸多态性（SNP，rs1121980、rs72803657和rs4783818）进行基因分型，以研究FTO基因多态性对个体患CAD易感性的影响。
利用聚合酶链反应-连接检测反应（PCR-LDR）技术，对712例CAD患者（其中349例心肌梗死（MI）患者）和701名对照参与者组成的队列进行了三个SNP（rs1121980、rs72803657和rs4783818）的基因分型。使用多因素逻辑回归分析这些SNP与CAD的关联，并通过Kruskal-Wallis检验或Wilcoxon-Mann-Whitney检验评估其与血脂谱的关联。
FTO rs1121980的A等位基因（比值比（OR）=1.26，95%置信区间（CI）=1.01-1.57，P=0.044）和AA基因型（OR=3.13，95%CI=1.53-6.38，P=0.002）与CAD风险升高显著相关。同样，rs1121980的A等位基因（OR=1.54，95%CI=1.18-2.02，P=0.002）和AA基因型（OR=5.61，95%CI=2.57-12.27，P<0.001）表现出MI风险增加。该SNP在CAD和MI的隐性遗传模型下也显示出显著关联（CAD的OR=3.09，95%CI=1.52-6.27，P=0.002；MI的OR=5.40，95%CI=2.49-11.71，P<0.001）。然而，在任何测试的遗传模型下，其他两个SNP与CAD或MI风险均未显示出显著关联。分层分析表明，在年轻参与者、非吸烟者和非饮酒者中，A等位基因与CAD/MI风险增加的关联更为明显。有趣
