A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients

Simon Vogel; Irina Rudaka; Dmitrijs Rots; Jekaterīna Isakova; Oskars Kalējs; Kristīne Vīksne; Linda Gailīte

doi:10.3390/medicina57111263

A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients

Medicina (Kaunas). 2021 Nov 18;57(11):1263. doi: 10.3390/medicina57111263.

Authors

Simon Vogel¹, Irina Rudaka^{1

2}, Dmitrijs Rots¹, Jekaterīna Isakova¹, Oskars Kalējs², Kristīne Vīksne¹, Linda Gailīte¹

Affiliations

¹ Scientific Laboratory of Molecular Genetics, Rīga Stradiņš University, 16 Dzirciema Str., LV-1007 Rīga, Latvia.
² Latvian Cardiology Center, Pauls Stradiņš Clinical University Hospital, Pilsoņu iela 13, Zemgales priekšpilsēta, LV-1002 Rīga, Latvia.

Abstract

Background and Objectives: Recurrence of atrial fibrillation (AF) within six months after sinus rhythm restoration with direct current cardioversion (DCC) is a significant treatment challenge. Currently, the factors influencing outcome are mostly unknown. Studies have found a link between genetics and the risk of AF and efficacy of rhythm control. The aim of this study was to examine the association between eight single-nucleotide variants (SNVs) and the risk of AF development and recurrence after DCC. Materials and Methods: Regarding the occurrence of AF, 259 AF cases and 108 controls were studied. Genotypes for the eight SNVs located in the genes CAV1, MYH7, SOX5, KCNN3, ZFHX3, KCNJ5 and PITX2 were determined using high-resolution melting analysis and confirmed with Sanger sequencing. Six months after DCC, a telephone interview was conducted to determine whether AF had recurred. A polygenic risk score (PRS) was calculated as the unweighted sum of risk alleles. Multivariate regression analyses were performed to assess SNV and PRS association with AF occurrence and recurrence after DCC. Results: The risk allele of rs2200733 (PITX2) was significantly associated with the development of AF (p = 0.012, OR = 2.31, 95% CI = 1.206-4.423). AF recurred in 60% of patients and the allele generally associated with a decreased risk of AF of rs11047543 (SOX5) was associated with a greater risk of AF recurrence (p = 0.014, OR = 0.223, 95% CI = 0.067-0.738). A PRS of greater than 7 was significantly associated (p = 0.008) with a higher likelihood of developing AF after DCC (OR = 4.174, 95% CI = 1.454-11.980). Conclusions: A higher PRS is associated with increased odds of AF recurrence after treatment with DCC. PITX2 (rs2200733) is significantly associated with an increased risk of AF. The protective allele of rs11047543 (SOX5) is associated with a greater risk of AF recurrence. Further studies are needed to predict the success of rhythm control and guide patient selection towards the most efficacious treatment.

Keywords: PITX2; SOX5; atrial fibrillation; direct current cardioversion; polygenic risk score.

MeSH terms

Atrial Fibrillation* / epidemiology
Atrial Fibrillation* / genetics
Atrial Fibrillation* / therapy
Electric Countershock*
Humans
Recurrence
Risk Factors
Small-Conductance Calcium-Activated Potassium Channels
Treatment Outcome

Substances

KCNN3 protein, human
Small-Conductance Calcium-Activated Potassium Channels