Abstract
Atrial fibrillation (AF) is the most common cardiac rhythm disorder at the clinical setting and accounts for up to 15% of all strokes. Recent genome-wide association studies (GWAS) identified two single nucleotide polymorphisms (SNPs), rs2106261 and rs7193343 in ZFHX3 (zinc finger homeobox 3 gene) and rs13376333 in KCNN3 (encoding a potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3) that showed significant association with AF in multiple populations of European ancestry. Here, we studied a Chinese Han, GeneID cohort consisting of 650 AF patients and 1,447 non-AF controls to test whether the GWAS findings on ZFHX3/KCNN3 and AF can be expanded to a different ethnic population. No significant association was detected for rs7193343 in ZFHX3 and rs13376333 in KCNN3. However, significant association was identified between rs2106261 in ZFHX3 and AF in the GeneID population for both allelic frequencies (P = 0.001 after adjusting for covariates of age, gender, hypertension, coronary artery disease, and diabetes mellitus; OR = 1.32), and genotypic frequencies assuming either an additive or recessive model (OR = 1.29, P = 0.001 and OR = 1.77, P = 0.00018, respectively). When only lone AF cases were analyzed, the association remained significant (OR = 1.50, P = 0.001 for allelic association; OR = 1.45, P = 0.001 for an additive model; OR = 2.24, P = 0.000043 for a recessive model). Our results indicate that rs2106261 in ZFHX3 confers a significant risk of AF in a Chinese Han population. The study expands the association between ZFHX3 and AF to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of the 16q22 AF locus.
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Acknowledgments
We thank the study participants for their important support of this research. We thank Dr Baofeng Yang for help and discussion. This study was supported by a Hubei Province Natural Science Key Program (2008CDA047), the China National Basic Research Program (973 Program 2007CB512002), a China National 863 Scientific Program (2006AA02Z476), a National Natural Science Foundation grant of China (30670857 and 30800457), a Key Academic Program Leader Award of Wuhan City (200951830560), and in part by an NIH grant (R01 HL094498). This study has no relationship with any industry.
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C. Li, F. Wang, Y. Yang and F. Fu contributed equally to this work.
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Li, C., Wang, F., Yang, Y. et al. Significant association of SNP rs2106261 in the ZFHX3 gene with atrial fibrillation in a Chinese Han GeneID population. Hum Genet 129, 239–246 (2011). https://doi.org/10.1007/s00439-010-0912-6
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DOI: https://doi.org/10.1007/s00439-010-0912-6