Cheng Liu1,2,3, Jingxian Pei4, Yanxian Lai5, Tianwang Guan6, Abudurexiti Zeyaweiding7, Tutiguli Maimaiti7, Haiyan Zhao7, Yan Shen6. 1. Department of Cardiology, Guangzhou First People's Hospital, South China University of Technology, 1 Panfu Road, Guangzhou, 510180, China. eyliucheng@scut.edu.cn. 2. Department of Cardiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China. eyliucheng@scut.edu.cn. 3. Department of Cardiology, Shufu People's Hospital, Kashgar Region, 844100, Xinjiang Uygur Autonomous Region (XUAR), China. eyliucheng@scut.edu.cn. 4. Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China. 5. Department of Cardiology, Guangzhou First People's Hospital, South China University of Technology, 1 Panfu Road, Guangzhou, 510180, China. 6. Department of Cardiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China. 7. Department of Cardiology, Shufu People's Hospital, Kashgar Region, 844100, Xinjiang Uygur Autonomous Region (XUAR), China.
Abstract
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Type 2 diabetes (T2D) is an independent risk factor for AF. The cardioembolic stroke (CS) risk is increased when both conditions coexist. Whether angiotensin-converting enzyme 2 (ACE2) genetic variants predict increased risks AF and CS in Uygur patients with T2D remain elusive. METHODS: A total of 547 Uygur subjects (272 controls and 275 T2D patients) were recruited to the study from south Xinjiang. Eight ACE2 variants were identified by MassARRAY system. RESULTS: ACE2 rs2074192 (CC, adjusted RR = 2.55, 95% CI 1.35-4.80, P = 0.004), rs4240157 (CC + CT, adjusted RR = 2.26, 95% CI 1.27-4.04, P = 0.006) and rs4646188 (TT, adjusted RR = 2.37, 95% CI 1.16-4.86, P = 0.018) were associated with higher AF risk. ACE2 rs4240157 (CC + CT, adjusted RR = 2.68, 95% CI 1.36-5.27, P = 0.004) and rs4646188 (TT, adjusted RR = 2.56, 95% CI 1.06-6.20, P = 0.037) were further associated with higher CS risk. The 3 ACE2 variants were related to larger left atrial end-systolic diameter (LAD) (all P < 0.05), but not all of the 3 ACE2 variants were related to increased levels of serum sodium (rs4240157 and rs4646188, all P < 0.05), HsCRP (rs4240157 and rs4646188, all P < 0.05) as well as decreased serum potassium levels (rs2074192 and rs4646188, all P < 0.05). The 3 ACE2 variants exhibited heterogeneity on circulating RAAS activation. In particular, ACE2 rs4646188 was associated with higher levels of ACE (P = 0.017 and 0.037), Ang I (P = 0.002 and 0.001), Ang II (both P < 0.001) and ALD (P = 0.005 and 0.011). CONCLUSION: These results indicated ACE2 rs4646188 was associated with increased risk of AF and CS among diabetic patients in Uygurs, which could be a promising genetic predisposition marker for early and personalized prevention strategies for the aforementioned clinical pathologies.
BACKGROUND:Atrial fibrillation (AF) is the most common cardiac arrhythmia. Type 2 diabetes (T2D) is an independent risk factor for AF. The cardioembolic stroke (CS) risk is increased when both conditions coexist. Whether angiotensin-converting enzyme 2 (ACE2) genetic variants predict increased risks AF and CS in Uygur patients with T2D remain elusive. METHODS: A total of 547 Uygur subjects (272 controls and 275 T2D patients) were recruited to the study from south Xinjiang. Eight ACE2 variants were identified by MassARRAY system. RESULTS:ACE2rs2074192 (CC, adjusted RR = 2.55, 95% CI 1.35-4.80, P = 0.004), rs4240157 (CC + CT, adjusted RR = 2.26, 95% CI 1.27-4.04, P = 0.006) and rs4646188 (TT, adjusted RR = 2.37, 95% CI 1.16-4.86, P = 0.018) were associated with higher AF risk. ACE2rs4240157 (CC + CT, adjusted RR = 2.68, 95% CI 1.36-5.27, P = 0.004) and rs4646188 (TT, adjusted RR = 2.56, 95% CI 1.06-6.20, P = 0.037) were further associated with higher CS risk. The 3 ACE2 variants were related to larger left atrial end-systolic diameter (LAD) (all P < 0.05), but not all of the 3 ACE2 variants were related to increased levels of serum sodium (rs4240157 and rs4646188, all P < 0.05), HsCRP (rs4240157 and rs4646188, all P < 0.05) as well as decreased serum potassium levels (rs2074192 and rs4646188, all P < 0.05). The 3 ACE2 variants exhibited heterogeneity on circulating RAAS activation. In particular, ACE2rs4646188 was associated with higher levels of ACE (P = 0.017 and 0.037), Ang I (P = 0.002 and 0.001), Ang II (both P < 0.001) and ALD (P = 0.005 and 0.011). CONCLUSION: These results indicated ACE2rs4646188 was associated with increased risk of AF and CS among diabeticpatients in Uygurs, which could be a promising genetic predisposition marker for early and personalized prevention strategies for the aforementioned clinical pathologies.
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