Abstract
BackgroundAtrial 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.MethodsA 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.ResultsACE2 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).ConclusionThese 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.
Highlights
Atrial fibrillation (AF) is the most common cardiac arrhythmia
All adult participants were diagnosed at baseline with Type 2 diabetes (T2D) referring to the American Diabetes Association (ADA) recommendations [16]: (1) a random serum glucose levels ≥ 11.1 mmol/L in a participant with symptoms of marked hyperglycemia including polyuria, polydipsia, polyphagia and weight loss; (2) a fasting plasma glucose (FPG) levels ≥ 7.0 mmol/L; (3) 2 h plasma glucose levels ≥ 11.1 mmol/L via oral glucose tolerance test (OGTT); (4) plasma glycosylated hemoglobin (HbA1C) concentration ≥ 6.5%
In subgroup of participants without T2D, none of the eight angiotensinconverting enzyme 2 (ACE2) variants was associated with AF risk
Summary
Type 2 diabetes (T2D) is an independent risk factor for AF. The cardioembolic stroke (CS) risk is increased when both conditions coexist. Whether angiotensinconverting enzyme 2 (ACE2) genetic variants predict increased risks AF and CS in Uygur patients with T2D remain elusive. Atrial fibrillation (AF) is the most common arrhythmia worldwide, and type 2 diabetes (T2D) is an independent risk factor for AF [1]. More Studies indicated that the risk of cardioembolic stroke (CS) is increased when both conditions coexist, becoming a major public health problem in China. Optimal glycemic management and integrated control of these reversible risk factors (e.g., unhealthy diet, smoking, physical inactivity, obesity, and obstructive sleep apnea syndrome, dyslipidemia, etc.) have been related to lower incidence of AF and CS, the benefit could be dampened or offset by inherently greater genetic risk [4]. Early genetic risk evaluation of individual’s at greater risk of AF and CS will provide a possible strategy for precision prevention of AF and CS in patients with T2D
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