Abstract 4405: Sequence Variant for Atrial Fibrillation on Chromosome 4q25 near the PITX2 Gene Increases Risk for Recurrent AF
Introduction. We have previously reported a strong association between two sequence variants on chromosome 4q25 and atrial fibrillation (AF) as the result of a genome-wide association study in Icelandic patients. This association has been replicated in three populations of European descent. About 35% of individuals of European descent have at least one of the variants and the risk of AF increases by 1.72 and 1.39 per copy for the two variants, rs 2200733 and rs10033464, respectively. The purpose of our current analysis was to examine the phenotypes of Icelandic AF patients in relation to the stronger sequence variant, rs2200733.
Methods. The patients had received the diagnosis of AF at Landspitali University Hospital in Iceland. A genome-wide association scan with 316,000 SNPs on a Illumina BeadChip was performed and medical records were utilized for phenotypic data collection.
Results. Our data set contained 719 cases with confirmed AF and detailed phenotypic/genotypic data, 435 men and 284 women. Thirty four were homozygous for the stronger genetic variant and 190 heterozygous. The mean age at diagnosis was 69.9 years in the non-carrier group and decreased by 1.9 years for each risk allele (p=0.018). There was a significantly stronger association with lone AF than with AF associated with hypertension or structural heart disease (p=0.042, OR 1.35). There was also a significantly stronger association with recurrent AF as opposed to single episode only (p=0.045, OR 1.47). There was no differential association with stroke but the incidence of stroke diagnosed at time of first presentation with atrial fibrillation was equal in the three groups of homozygous, heterozygous and non-carriers (5.9%, 5.3% and 5.3% respectively) despite younger age of the homozygous individuals.
Conclusions. Previous analysis demonstrates that the sequence variant rs2200733 is a strong risk factor for AF. This analysis shows that carriers are diagnosed at a younger age and are less likely to have other common AF risk factors such as hypertension and structural heart disease, although the variant increases the risk of AF in all sub-phenotypes. Furthermore, carriers appear more prone to develop recurrent AF.