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Angiotensinogen gene polymorphisms predictive of stroke in AF
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Polymorphisms in the angiotensinogen gene may be predictive of stroke among patients with atrial fibrillation, according to recent findings.
In a longitudinal follow-up study, researchers evaluated 712 consecutive patients diagnosed with AF at National Taiwan University Hospital and National Taiwan University Hospital Yun Lin Branch. Study participants were diagnosed after January 1998 and underwent a median of 10.3 years of follow-up. Patients had persistent AF in 69% of cases.
All patients received transthoracic ECG to obtain left atrial and left ventricular measurements, as well as to assess LV ejection fraction and identify the presence of significant valvular disease. The researchers performed genotyping of the ACE gene, AT1R gene A1166C and angiotensinogen gene polymorphisms. Eight polymorphisms were identified, six of which were in the angiotensinogen gene. Haplotype analysis was performed to establish the overall effect of these polymorphisms; specifically, their association with stroke risk.
Of the evaluated polymorphisms, researchers only observed an association between stroke risk and the G-6A polymorphism of the AGT gene. Patients with one or more G-6 alleles were significantly more likely to develop stroke than those without G-6 alleles (P=.006). This increased risk remained significant after adjustment for confounders (HR=2.54; 95% CI, 1.26-5.12).
The addition of G-6A genotype information to the CHADS2 risk scheme for analyzing stroke events increased the area under the receiver operating characteristic curve from 0.672 (95% CI, 0.641-0.705) for CHADS2 alone to 0.724 (95% CI, 0.7-0.749).
Haplotype analysis revealed that gene promoter haplotypes containing G-217 and G-6 alleles were significantly associated with stroke (P<.05). Patients with at least one of these haplotypes were more likely to experience stroke than those without them (P=.001). Multivariable adjustment indicated a significantly increased stroke risk among G-217/G-6 carriers (HR=2.78; 95% CI, 1.37-5.64).
Researchers noted that the link between G allele carriers and stroke only occurred among patients who did not undergo long-term therapy with ACE inhibitors or angiotensin receptor blockers (P=.009). Multivariable adjustment indicated an increased risk for stroke among those not treated with these medications (HR=2.65; 95% CI, 1.29-5.44), and a significant interaction was observed between G-6A polymorphism and treatment on stroke risk (P=.12)
“Our long-term prospective observation study showed that AF patients with the genetic ground of a higher AGT gene promoter activity have a higher risk to develop stroke,” the researchers concluded. “… We do not propose that the result of genotyping be incorporated in to the CHADS2 or CHADS2-Vasc scheme to determine whether patients should receive anticoagulation or not, but suggest that for those with high-risk genotypes, the prescription of [ACE inhibitors or angiotensin receptor blockers] … is recommended.”
Disclosure: The researchers report no relevant financial disclosures.
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