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.
Ren
Xiang
X
Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, PR China.
Xu
Chengqi
C
Zhan
Chengxiong
C
Yang
Yanzong
Y
Shi
Lisong
L
Wang
Fan
F
Wang
Chuchu
C
Xia
Yunlong
Y
Yang
Bo
B
Wu
Gang
G
Wang
Pengyun
P
Li
Xiuchun
X
Wang
Dan
D
Xiong
Xin
X
Liu
Jinqiu
J
Liu
Ying
Y
Liu
Mugen
M
Liu
Jingyu
J
Tu
Xin
X
Wang
Qing Kenneth
QK
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000235:genetics*; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D002681:China; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C472955:NPPA protein, human; D009320:Atrial Natriuretic Factor