Key result
The ACE2 rs4646188 TT genotype was associated with a significantly increased risk of new-onset atrial fibrillation (adjusted RR 2.37) and cardioembolic stroke in Uygur patients with type 2 diabetes.
Why the study?
Whether ACE2 genetic variants predict increased risks of AF and cardioembolic stroke in Uygur patients with T2D remained elusive.
Do ACE2 genetic variants increase the risk of new-onset atrial fibrillation and cardioembolic stroke in Uygur patients with type 2 diabetes?
Cohort (n=547)
No
Do ACE2 genetic variants increase the risk of new-onset atrial fibrillation and cardioembolic stroke in Uygur patients with type 2 diabetes?
The ACE2 rs4646188 variant is a promising genetic marker for predicting increased risk of atrial fibrillation and cardioembolic stroke in Uygur patients with type 2 diabetes.
May support risk stratification in Uygur T2D; leaves open generalizability and need for prospective validation.
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.
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Liu et al. (2021) conducted a cohort in Type 2 diabetes (n=547). ACE2 variant rs4646188 (TT genotype) vs. ACE2 variant rs4646188 (CC + CT genotypes) was evaluated on New-onset atrial fibrillation (adjusted RR 2.37, 95% CI 1.16-4.86, p=0.018). The ACE2 rs4646188 TT genotype was associated with a significantly increased risk of new-onset atrial fibrillation (adjusted RR 2.37) and cardioembolic stroke in Uygur patients with type 2 diabetes.
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