Significant association of SNP rs2106261 in the ZFHX3 gene with atrial fibrillation in a Chinese Han GeneID population

Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China.
Human Genetics (Impact Factor: 4.82). 03/2011; 129(3):239-46. DOI: 10.1007/s00439-010-0912-6
Source: PubMed


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.

27 Reads
  • Source
    • "The SNPs located at 16q22 are intronic for ZFHX3, a transcription factor with unknown cardiac involvement. It has been hypothesized that ZFHX3 may be a regulatory factor for the JAK/STAT signaling cascade and this cascade may be involved in atrial fibrillation susceptibility; however, further study is needed to clarify this relationship [44], [45]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite a greater burden of risk factors, atrial fibrillation (AF) is less common among African Americans than European-descent populations. Genome-wide association studies (GWAS) for AF in European-descent populations have identified three predominant genomic regions associated with increased risk (1q21, 4q25, and 16q22). The contribution of these loci to AF risk in African American is unknown. We studied 73 African Americans with AF from the Vanderbilt-Meharry AF registry and 71 African American controls, with no history of AF including after cardiac surgery. Tests of association were performed for 148 SNPs across the three regions associated with AF, and 22 SNPs were significantly associated with AF (P<0.05). The SNPs with the strongest associations in African Americans were both different from the index SNPs identified in European-descent populations and independent from the index European-descent population SNPs (r(2)<0.40 in HapMap CEU): 1q21 rs4845396 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.13-0.67, P = 0.003), 4q25 rs4631108 (OR 3.43, 95% CI 1.59-7.42, P = 0.002), and 16q22 rs16971547 (OR 8.1, 95% CI 1.46-45.4, P = 0.016). Estimates of European ancestry were similar among cases (23.6%) and controls (23.8%). Accordingly, the probability of having two copies of the European derived chromosomes at each region did not differ between cases and controls. Variable European admixture at known AF loci does not explain decreased AF susceptibility in African Americans. These data support the role of 1q21, 4q25, and 16q22 variants in AF risk for African Americans, although the index SNPs differ from those identified in European-descent populations.
    PLoS ONE 02/2012; 7(2):e32338. DOI:10.1371/journal.pone.0032338 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibrillation (AF) affects more than 5 million people worldwide; however, none of the anti-arrhythmic drugs available now are entirely optimal in terms of efficacy and safety. A better understanding of the molecular mechanism of AF will facilitate the process of finding new strategies to prevent AF. As the non-familial AF is the major form of AF, identifying common variants for AF in these populations by genome-wide association studies will definitely accelerate this process. This review summarizes the recently identified common AF variants on 4q25, 16q22, and 1q21 and discusses their implications for the clinic.
    Human Genetics 07/2011; 131(1):33-9. DOI:10.1007/s00439-011-1052-3 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A recent study in individuals of European ancestry demonstrated a significant association of the single nucleotide polymorphism (SNP) rs13376333 in potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3 (KCNN3) on chromosome 1q21 with lone atrial fibrillation (AF), indicating a common genetic basis for AF. The aim of the present study was to investigate whether this association between SNP rs13376333 and AF also exists in Taiwanese subjects. The SNP rs13376333 was compared in 214 lone AF patients (58.3±11.4 years) vs. 214 controls (57.7±13.2 years), and in 322 structural AF patients (69.6±13.7 years) vs. 322 controls (68.4±14.2 years) in a Taiwanese population, in a case-control design. The associations between SNP rs13376333 in KCNN3 and structural or lone AF were significant. In the lone AF group, the frequency of the minor allele of SNP rs13376333 was 8.6% compared with 3.0% in the controls (P<0.001; odds ratio [OR], 3.02; 95% confidence interval [CI]: 1.54-6.29). The frequency of the minor allele of SNP rs13376333 was 6.5% in structural AF patients compared with 3.1% in controls (P=0.004; OR, 2.18; 95%CI: 1.23-3.96). There are significant associations between SNP rs13376333 and the risk of developing both lone and structural AF in the Taiwanese population. The minor allele frequency of SNP rs13376333 was much lower in the Taiwanese population compared to that in the Caucasian population.
    Circulation Journal 01/2012; 76(1):184-8. DOI:10.4020/jhrs.27.BPB_2 · 3.94 Impact Factor
Show more