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

<i>Background and Objectives</i>: 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...

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Autores principales:	Simon Vogel, Irina Rudaka, Dmitrijs Rots, Jekaterīna Isakova, Oskars Kalējs, Kristīne Vīksne, Linda Gailīte
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	atrial fibrillation <i>PITX2</i> <i>SOX5</i> polygenic risk score direct current cardioversion Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/238f1be2d535434f866066c1b5f15f59
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spelling	oai:doaj.org-article:238f1be2d535434f866066c1b5f15f592021-11-25T18:19:03ZA Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients10.3390/medicina571112631648-91441010-660Xhttps://doaj.org/article/238f1be2d535434f866066c1b5f15f592021-11-01T00:00:00Zhttps://www.mdpi.com/1648-9144/57/11/1263https://doaj.org/toc/1010-660Xhttps://doaj.org/toc/1648-9144<i>Background and Objectives</i>: 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. <i>Materials and Methods:</i> Regarding the occurrence of AF, 259 AF cases and 108 controls were studied. Genotypes for the eight SNVs located in the genes <i>CAV1</i>, <i>MYH7</i>, <i>SOX5</i>, <i>KCNN3</i>, <i>ZFHX3</i>, <i>KCNJ5</i> and <i>PITX2</i> 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. <i>Results:</i> The risk allele of rs2200733 (<i>PITX2</i>) was significantly associated with the development of AF (<i>p</i> = 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 (<i>SOX5</i>) was associated with a greater risk of AF recurrence (<i>p</i> = 0.014, OR = 0.223, 95% CI = 0.067–0.738). A PRS of greater than 7 was significantly associated (<i>p</i> = 0.008) with a higher likelihood of developing AF after DCC (OR = 4.174, 95% CI = 1.454–11.980). <i>Conclusions</i>: A higher PRS is associated with increased odds of AF recurrence after treatment with DCC. <i>PITX2</i> (rs2200733) is significantly associated with an increased risk of AF. The protective allele of rs11047543 (<i>SOX5</i>) 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.Simon VogelIrina RudakaDmitrijs RotsJekaterīna IsakovaOskars KalējsKristīne VīksneLinda GailīteMDPI AGarticleatrial fibrillation<i>PITX2</i><i>SOX5</i>polygenic risk scoredirect current cardioversionMedicine (General)R5-920ENMedicina, Vol 57, Iss 1263, p 1263 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	atrial fibrillation <i>PITX2</i> <i>SOX5</i> polygenic risk score direct current cardioversion Medicine (General) R5-920
spellingShingle	atrial fibrillation <i>PITX2</i> <i>SOX5</i> polygenic risk score direct current cardioversion Medicine (General) R5-920 Simon Vogel Irina Rudaka Dmitrijs Rots Jekaterīna Isakova Oskars Kalējs Kristīne Vīksne Linda Gailīte A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients
description	<i>Background and Objectives</i>: 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. <i>Materials and Methods:</i> Regarding the occurrence of AF, 259 AF cases and 108 controls were studied. Genotypes for the eight SNVs located in the genes <i>CAV1</i>, <i>MYH7</i>, <i>SOX5</i>, <i>KCNN3</i>, <i>ZFHX3</i>, <i>KCNJ5</i> and <i>PITX2</i> 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. <i>Results:</i> The risk allele of rs2200733 (<i>PITX2</i>) was significantly associated with the development of AF (<i>p</i> = 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 (<i>SOX5</i>) was associated with a greater risk of AF recurrence (<i>p</i> = 0.014, OR = 0.223, 95% CI = 0.067–0.738). A PRS of greater than 7 was significantly associated (<i>p</i> = 0.008) with a higher likelihood of developing AF after DCC (OR = 4.174, 95% CI = 1.454–11.980). <i>Conclusions</i>: A higher PRS is associated with increased odds of AF recurrence after treatment with DCC. <i>PITX2</i> (rs2200733) is significantly associated with an increased risk of AF. The protective allele of rs11047543 (<i>SOX5</i>) 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.
format	article
author	Simon Vogel Irina Rudaka Dmitrijs Rots Jekaterīna Isakova Oskars Kalējs Kristīne Vīksne Linda Gailīte
author_facet	Simon Vogel Irina Rudaka Dmitrijs Rots Jekaterīna Isakova Oskars Kalējs Kristīne Vīksne Linda Gailīte
author_sort	Simon Vogel
title	A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients
title_short	A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients
title_full	A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients
title_fullStr	A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients
title_full_unstemmed	A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients
title_sort	higher polygenic risk score is associated with a higher recurrence rate of atrial fibrillation in direct current cardioversion-treated patients
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/238f1be2d535434f866066c1b5f15f59
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A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients

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