This author interview is by Dr. Hirad Yarmohammadi, of Johns Hopkins University.  Dr. Yarmohammadi’s full paper, Association of Common Variations on Chromosome 4q25 and Left Atrial Volume in Patients with Atrial Fibrillation, is available for download in Clinical Medicine Insights: Cardiology.

Please summarize for readers the content of your article.
We prospectively enrolled 96 consecutive patients (mean age 60 ± 10 years, 72% male) with drug-resistant atrial fibrillation who underwent catheter ablation to investigate the association of SNPs rs10033464 and rs2200733 near the PITX2 locus on 4q25 and left atrial volume (measured by CT or MRI). We found that homozygosity for the minor allele at rs10033464 (recessive model) was independently associated with larger left atrial volume (P = 0.002) after adjustment for the potential confounders. In contrast, no association was found between rs2200733 variant alleles and left atrial volume. 

How did you come to be involved in your area of study?
Initially, I was introduced to the concept through my mentor Dr. Nazarian at Johns Hopkins University. Based on what we already know, we designed the method to examine our hypothesis as it presented in the paper.

What was previously known about the topic of your article?
Recent genome-wide association analyses have identified multiple loci that are associated with atrial fibrillation. One of the strongest associations with AF involves two non-coding SNPs on chromosome 4q25 (rs2200733 and rs10033464). Both SNPs were also found to be associated with increased risk of AF recurrence after catheter ablation, elevated risk of cardioembolic stroke, and development of AF after coronary artery bypass grafting.

Interestingly, both SNPs are adjacent to the PITX2 gene, which has a major role in cardiac development and its reduced expression have been shown to be associated with progressive enlargement of the left atrium in animal model.

How has your work in this area advanced understanding of the topic?
To date, data in humans possessing the high risk variants near PITX2 gene or other genomic elements in the region are sparse and the underlying pathophysiology at these loci is unknown. Nevertheless, our findings might catalyze the exploration of new molecular pathways underlying AF.

What do you regard as being the most important aspect of the results reported in the article?
This is the first report of an association in humans between a SNP in close proximity to the PITX2 gene with left atrial structure in patients with AF. These findings would lead us to the better understanding of the pathophysiology of atrial fibrillation and the role of the SNPs in development and progression of the disease.

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