Association of common variations on chromosome 4q25 and left atrial volume in patients with atrial fibrillation

Yuliya Mints, Hirad Yarmohammadi, Irfan M. Khurram, Hana Hoyt, Rozann Hansford, Stefan Zimmerman, Steven J. Steinberg, Daniel P. Judge, Gordon F. Tomaselli, Hugh Calkins, Vadim Zipunnikov, Saman Nazarian

Research output: Contribution to journalArticle

Abstract

Aims: Recent studies have shown that several genetic variants near the PITX2 locus on chromosome 4q25 are associated with atrial fibrillation (AF). However, the mechanism that mediates this association remains unclear. Basic murine studies suggest that reduced PITX2 expression is associated with left atrial dilatation. We sought to examine the association between single nucleotide polymorphisms (SNPs) near PITX2 and left atrial size in patients with AF. Methods: We prospectively enrolled 96 consecutive patients (mean age 60 ± 10 years, 72% male) with drug-resistant AF (57% paroxysmal, 38% persistent, and 5% long-standing persistent) who underwent catheter ablation. Following DNA extraction from blood obtained pre-operatively, SNPs rs10033464 and rs2200733 were genotyped using the Sequenom MassARRAY. Left atrial volume (LAV) was determined using three-dimensional imaging (CT or MRI prior to first ablation) and by investigators blinded to genotype results. Results: The minor allele frequencies at SNPs rs10033464 and rs2200733 were 0.14 and 0.25, respectively. Using multivariable linear regression, homozygosity for the minor allele at rs10033464 (recessive model) was independently associated with larger LAV (P = 0.002) after adjustment for age, gender, BMI, height, type, and duration of AF, left ventricular ejection fraction, history of hypertension, valve disease, and antiarrhythmic drug use. The strength of the association was reconfirmed in a bootstrap study with 1000 resamplings. In contrast, no association was found between rs2200733 variant alleles and LAV. Conclusion: SNP rs10033464 near the PITX2 locus on 4q25 is associated with LAV. Left atrial dilatation may mediate the association of common variants at 4q25 with AF.

Original languageEnglish (US)
Pages (from-to)39-45
Number of pages7
JournalClinical Medicine Insights: Cardiology
Volume9
DOIs
StatePublished - May 13 2015

Fingerprint

Atrial Fibrillation
Chromosomes
Single Nucleotide Polymorphism
Dilatation
Alleles
Catheter Ablation
Three-Dimensional Imaging
Anti-Arrhythmia Agents
Gene Frequency
Stroke Volume
Linear Models
Genotype
Research Personnel
Hypertension
DNA
Pharmaceutical Preparations

Keywords

  • Atrial fibrillation
  • Catheter ablation
  • Left atrium volume
  • PITX2
  • Single nuclear polymorphisms

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Association of common variations on chromosome 4q25 and left atrial volume in patients with atrial fibrillation. / Mints, Yuliya; Yarmohammadi, Hirad; Khurram, Irfan M.; Hoyt, Hana; Hansford, Rozann; Zimmerman, Stefan; Steinberg, Steven J.; Judge, Daniel P.; Tomaselli, Gordon F.; Calkins, Hugh; Zipunnikov, Vadim; Nazarian, Saman.

In: Clinical Medicine Insights: Cardiology, Vol. 9, 13.05.2015, p. 39-45.

Research output: Contribution to journalArticle

Mints, Yuliya ; Yarmohammadi, Hirad ; Khurram, Irfan M. ; Hoyt, Hana ; Hansford, Rozann ; Zimmerman, Stefan ; Steinberg, Steven J. ; Judge, Daniel P. ; Tomaselli, Gordon F. ; Calkins, Hugh ; Zipunnikov, Vadim ; Nazarian, Saman. / Association of common variations on chromosome 4q25 and left atrial volume in patients with atrial fibrillation. In: Clinical Medicine Insights: Cardiology. 2015 ; Vol. 9. pp. 39-45.
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abstract = "Aims: Recent studies have shown that several genetic variants near the PITX2 locus on chromosome 4q25 are associated with atrial fibrillation (AF). However, the mechanism that mediates this association remains unclear. Basic murine studies suggest that reduced PITX2 expression is associated with left atrial dilatation. We sought to examine the association between single nucleotide polymorphisms (SNPs) near PITX2 and left atrial size in patients with AF. Methods: We prospectively enrolled 96 consecutive patients (mean age 60 ± 10 years, 72{\%} male) with drug-resistant AF (57{\%} paroxysmal, 38{\%} persistent, and 5{\%} long-standing persistent) who underwent catheter ablation. Following DNA extraction from blood obtained pre-operatively, SNPs rs10033464 and rs2200733 were genotyped using the Sequenom MassARRAY. Left atrial volume (LAV) was determined using three-dimensional imaging (CT or MRI prior to first ablation) and by investigators blinded to genotype results. Results: The minor allele frequencies at SNPs rs10033464 and rs2200733 were 0.14 and 0.25, respectively. Using multivariable linear regression, homozygosity for the minor allele at rs10033464 (recessive model) was independently associated with larger LAV (P = 0.002) after adjustment for age, gender, BMI, height, type, and duration of AF, left ventricular ejection fraction, history of hypertension, valve disease, and antiarrhythmic drug use. The strength of the association was reconfirmed in a bootstrap study with 1000 resamplings. In contrast, no association was found between rs2200733 variant alleles and LAV. Conclusion: SNP rs10033464 near the PITX2 locus on 4q25 is associated with LAV. Left atrial dilatation may mediate the association of common variants at 4q25 with AF.",
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T1 - Association of common variations on chromosome 4q25 and left atrial volume in patients with atrial fibrillation

AU - Mints, Yuliya

AU - Yarmohammadi, Hirad

AU - Khurram, Irfan M.

AU - Hoyt, Hana

AU - Hansford, Rozann

AU - Zimmerman, Stefan

AU - Steinberg, Steven J.

AU - Judge, Daniel P.

AU - Tomaselli, Gordon F.

AU - Calkins, Hugh

AU - Zipunnikov, Vadim

AU - Nazarian, Saman

PY - 2015/5/13

Y1 - 2015/5/13

N2 - Aims: Recent studies have shown that several genetic variants near the PITX2 locus on chromosome 4q25 are associated with atrial fibrillation (AF). However, the mechanism that mediates this association remains unclear. Basic murine studies suggest that reduced PITX2 expression is associated with left atrial dilatation. We sought to examine the association between single nucleotide polymorphisms (SNPs) near PITX2 and left atrial size in patients with AF. Methods: We prospectively enrolled 96 consecutive patients (mean age 60 ± 10 years, 72% male) with drug-resistant AF (57% paroxysmal, 38% persistent, and 5% long-standing persistent) who underwent catheter ablation. Following DNA extraction from blood obtained pre-operatively, SNPs rs10033464 and rs2200733 were genotyped using the Sequenom MassARRAY. Left atrial volume (LAV) was determined using three-dimensional imaging (CT or MRI prior to first ablation) and by investigators blinded to genotype results. Results: The minor allele frequencies at SNPs rs10033464 and rs2200733 were 0.14 and 0.25, respectively. Using multivariable linear regression, homozygosity for the minor allele at rs10033464 (recessive model) was independently associated with larger LAV (P = 0.002) after adjustment for age, gender, BMI, height, type, and duration of AF, left ventricular ejection fraction, history of hypertension, valve disease, and antiarrhythmic drug use. The strength of the association was reconfirmed in a bootstrap study with 1000 resamplings. In contrast, no association was found between rs2200733 variant alleles and LAV. Conclusion: SNP rs10033464 near the PITX2 locus on 4q25 is associated with LAV. Left atrial dilatation may mediate the association of common variants at 4q25 with AF.

AB - Aims: Recent studies have shown that several genetic variants near the PITX2 locus on chromosome 4q25 are associated with atrial fibrillation (AF). However, the mechanism that mediates this association remains unclear. Basic murine studies suggest that reduced PITX2 expression is associated with left atrial dilatation. We sought to examine the association between single nucleotide polymorphisms (SNPs) near PITX2 and left atrial size in patients with AF. Methods: We prospectively enrolled 96 consecutive patients (mean age 60 ± 10 years, 72% male) with drug-resistant AF (57% paroxysmal, 38% persistent, and 5% long-standing persistent) who underwent catheter ablation. Following DNA extraction from blood obtained pre-operatively, SNPs rs10033464 and rs2200733 were genotyped using the Sequenom MassARRAY. Left atrial volume (LAV) was determined using three-dimensional imaging (CT or MRI prior to first ablation) and by investigators blinded to genotype results. Results: The minor allele frequencies at SNPs rs10033464 and rs2200733 were 0.14 and 0.25, respectively. Using multivariable linear regression, homozygosity for the minor allele at rs10033464 (recessive model) was independently associated with larger LAV (P = 0.002) after adjustment for age, gender, BMI, height, type, and duration of AF, left ventricular ejection fraction, history of hypertension, valve disease, and antiarrhythmic drug use. The strength of the association was reconfirmed in a bootstrap study with 1000 resamplings. In contrast, no association was found between rs2200733 variant alleles and LAV. Conclusion: SNP rs10033464 near the PITX2 locus on 4q25 is associated with LAV. Left atrial dilatation may mediate the association of common variants at 4q25 with AF.

KW - Atrial fibrillation

KW - Catheter ablation

KW - Left atrium volume

KW - PITX2

KW - Single nuclear polymorphisms

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