title: α-Kinase 2 is a novel candidate gene for inherited hypertension in Dahl rats.
abstract: OBJECTIVE
  The interval harboring a quantitative trait locus for blood pressure (BP), C18QTL3, contains β-2 adrenergic receptor (Adrb2) and neural precursor cell expressed, developmentally downregulated 4-like (Nedd4l) genes. None of the other genes in the C18QTL3-residing interval is known to affect BP. The identification of C18QTL3 might uncover a brand new gene that could prosper into a novel diagnostic and/or therapeutic target for essential hypertension, if neither Adrb2 nor Nedd4l could be upheld as candidate genes.
  
  
  METHODS
  Congenic fine resolution was combined with gene analyses.
  
  
  RESULTS
  The gene encoding α-kinase 2 (Alpk2) contains a three base-pair deletion and multiple nonconserved mutations in its coding region in Dahl salt-sensitive (DSS) rats. In contrast, the gastrin-releasing peptide gene (Grp) possesses two nonconserved mutations, designated as single nucleotide polymorphisms 1 and 2 (i.e. SNP1 and SNP2), but could not be supported as a candidate gene because the C18S.L14 congenic strain displayed a homozygous DSS genotype at both SNP1 and SNP2. Furthermore, Adrb2 and Nedd4l could not account for the BP-diminishing effect of Lewis alleles in C18S.L14, as their DSS alleles bear functionally identical domains as those of Lewis, and no evidence of differential expression and splicing was evident. No significant nucleotide variations were found in 13 other genes closely linked to Alpk2.
  
  
  CONCLUSIONS
  Alpk2 emerged as a strong candidate gene for C18QTL3. The present study is the first to implicate Alpk2 in the genetics of polygenic hypertension and paves the way for novel gene discovery.
authors: Department of Medicine, Research Centre, Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada.
authors: Cristina
authors: C
authors: Chauvet
authors: Kimberley
authors: K
authors: Crespo
authors: Annie
authors: A
authors: Ménard
authors: Yanrui
authors: Y
authors: Wu
authors: Chunjie
authors: C
authors: Xiao
authors: Marilyne
authors: M
authors: Blain
authors: Julie
authors: J
authors: Roy
authors: Alan Y
authors: AY
authors: Deng