Identification of NPPA variants associated with atrial fibrillation in a Chinese GeneID population

Background: A frameshift mutation in the NPPA gene was identified in 1 family with atrial fibrillation (AF), however, further studies are needed to establish unequivocally the genetic association between NPPA and AF. Methods: A case control association study and mutational analysis of NPPA were performed with 384 sporadic AF patients and 844 controls from a Chinese GeneID population. Genotyping was performed using High-Resolution Melt analysis. Mutational analysis was performed using direct DNA sequencing analysis. Results: Significant allelic association was detected between single nucleotide polymorphism (SNP) rs5063 and lone AF (p=0.015, OR=1.63; adjusted p=0.003). Genotypic association was significant assuming an additive or dominant model (adjusted p=0.005 and 0.007, respectively). Six new variants were identified in NPPA, including 2 in the 5'-UTR, 2 in the 3'-UTR, and 2 missense substitutions. Variants c.413T>C, c.*48G>A and c.*133G>T were not present in 844 controls, and the others were identified in controls. Conclusions: Variants in NPPA confer risk of lone AF in a Chinese population. Thus, in addition to being a disease-causing gene with mutations identified in familial AF cases, NPPA is a susceptibility gene for lone AF. (C) 2010 Elsevier B.V. All rights reserved.