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

BackgroundA 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.MethodsA 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.ResultsSignificant 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.ConclusionsVariants 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.