Abstract

Background Atrial fibrillation (AF) is a prevalent clinical condition worldwide, with a high global incidence that significantly impacts disease burden and mortality rates. Single nucleotide polymorphisms in ABCB1, ABCG2 and CYP3A5 are common, but the clinical outcomes are poorly understood. This study examines the association between the genetic variations of ABCB1, ABCG2 and CYP3A5 and the risk of AF in a Taiwanese population.

Methods This case-control study recruited 216 AF patients from two hospitals in Taiwan between 2021 and 2023. Control groups were matched by age (± one year), gender, and AF-related variables from the Taiwan Biobank. Logistic regression analyzed the association between three genetic variants and AF risk.

Results A significant association was noted between ABCG2 rs2231142 and AF risk. Those with ABCG2 rs2231142 G/T and T/T genotypes had a 1.91-fold (95% CI = 1.04-3.53) increased risk of AF compared to those with the G/G genotype. This association was particularly pronounced in males in those carrying ABCG2 rs2231143 T/T genotype having a 4.47-fold (95% CI = 1.02-19.67) increased risk after adjusting for covariates. There were no overall significant associations between AF risk and the polymorphisms of ABCB1 rs4148738 and rs1128503, nor CYP3A5 rs776746.

Conclusion A robust risk association between the ABCG2 rs2231142 T allele and AF in Asian populations, particularly in male adults, suggests that genetic testing for this polymorphism could be integrated into risk assessment models for AF.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

The study design was approved by the institutional review board of Kaohsiung Medical University Hospital (KMUHIRB-G(I)-20200040).

Funding Statement

This work was supported by grants from Kaohsiung Medical University Hospital (KMUH108-8R71), Kaohsiung Medical University Research Center Grant (KMU-TC108A01), from the Integrative Project of National Health Research Institutes and Kaohsiung Medical University (NHRIKMU-111-I005), Ministry of Science and Technology (MOST 108-2638-B-037-001-MY2).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study design was approved by the institutional review board of Kaohsiung Medical University Hospital (KMUHIRB-G(I)-20200040).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Data Availability

The data are not publicly available due to the nature of information that could compromise the privacy of research participants.

Nonstandard Abbreviations and Acronyms1000Genomes1000 Genomes ProjectAFAtrial fibrillationABCB1Adenosine triphosphate binding cassette subfamily B member 1ABCG2ATP-binding cassette subfamily G member 2ATPaseAdenosine triphosphataseBCRPBreast cancer resistance proteinCYP3A5Cytochrome P450 family 3 subfamily A member 5CYP450Cytochrome P450 proteinsDOACsDirect oral anticoagulantsGBD 2017Global Burden of Disease Study 2017gnomADGenome Aggregation DatabaseGWASGenome-Wide Association StudiesHbA1CGlycated hemoglobinIRBInstitutional Review BoardKMUHKaohsiung Medical University HospitalKMTTHKaohsiung Municipal Ta-Tung HospitalLDLLow-density lipoprotein cholesterolMYOZ1Myozenin 1P-gpP-glycoproteinPITX2Paired like homeodomain 2SNPsSingle Nucleotide PolymorphismsTGTriglycerideTWBTaiwan BiobankZFHX3Zinc finger homeobox 3