title: A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation.
abstract: The inward rectifier K(+) channel Kir2.1 mediates the potassium I(K1) current in the heart. It is encoded by KCNJ2 gene that has been linked to Andersen's syndrome. Recently, strong evidences showed that Kir2.1 channels were associated with mouse atrial fibrillation (AF), therefore we hypothesized that KCNJ2 was associated with familial AF. Thirty Chinese AF kindreds were evaluated for mutations in KCNJ2 gene. A valine-to-isoleucine mutation at position 93 (V93I) of Kir2.1 was found in all affected members in one kindred. This valine and its flanking sequence is highly conserved in Kir2.1 proteins among different species. Functional analysis of the V93I mutant demonstrated a gain-of-function consequence on the Kir2.1 current. This effect is opposed to the loss-of-function effect of previously reported mutations in Andersen's syndrome. Kir2.1 V93I mutation may play a role in initiating and/or maintaining AF by increasing the activity of the inward rectifier K(+) channel.
authors.affiliation: Institute of Medical Genetics, Tongji University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Jin
authors.forename: Saïd
authors.initials: S
authors.lastname: Bendahhou
authors.forename: Yusong
authors.initials: Y
authors.lastname: He
authors.forename: Marie-Madeleine
authors.initials: MM
authors.lastname: Larroque
authors.forename: Yiping
authors.initials: Y
authors.lastname: Chen
authors.forename: Qinshu
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Ban
authors.initials: B
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhu
authors.forename: Yanting
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xiongjian
authors.initials: X
authors.lastname: Dong
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Pan
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wang
authors.forename: Haiying
authors.initials: H
authors.lastname: Wan
authors.forename: Weiqin
authors.initials: W
authors.lastname: Qiu
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Xu
authors.forename: Petra
authors.initials: P
authors.lastname: Eurlings
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.forename: Yihan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics*; D019556:COS Cells; D002460:Cell Line; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry; D004252:DNA Mutational Analysis; D004594:Electrophysiology; D005192:Family Health; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D007532:Isoleucine / Q000737:chemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011487:Protein Conformation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014162:Transfection; D014633:Valine / Q000737:chemistry
chemical_list: C489457:KCNJ2 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D007532:Isoleucine; D004247:DNA; D014633:Valine