Association of ACE2 variant rs4646188 with the risks of atrial fibrillation and cardioembolic stroke in Uygur patients with type 2 diabetes

Abstract

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.