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

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. 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. 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. 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.