Premium
Genome‐wide association mapping of vasoreactivity in thoracic aorta from inbred mice
Author(s) -
Kim Seung Kyum,
Avila Joshua J.,
Massett Michael P.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1212.13
Subject(s) - quantitative trait locus , snp , phenylephrine , ec50 , genome wide association study , sodium nitroprusside , inbred strain , single nucleotide polymorphism , biology , strain (injury) , genetics , medicine , endocrinology , anatomy , genotype , gene , in vitro , blood pressure , nitric oxide
There are large strain‐dependent variations in vascular function in mice. However, the genetic factors underlying these variations are undefined. Therefore, the aim of this study was to identify novel putative quantitative trait loci (QTL) regulating vascular function. Vasoreactivity in thoracic aorta from inbred mice was measured and genome wide association mapping (GWA) was performed. Concentration response curves to phenylephrine (PE), potassium chloride (KCl), acetylcholine (ACh), and sodium nitroprusside (SNP) were obtained from aortic rings from male mice (n =4~8/strain) from 18 classical and wild‐derived strains. Maximal responses (MR) and half maximal effective concentrations (EC50) were calculated. GWA was performed for MR and EC50 using an efficient mixed‐model association algorithm (EMMA). Significant strain‐dependent differences were found for both MR and EC50 for each agent, except for MR for SNP. Significant QTL (P<3.79 × 10 −7 ; Bonferroni correction) were identified for MR for PE, ACh, and KCl and EC50 for SNP and KCl on several chromosomes (Chr). Common QTL between MR for ACh and EC50 for SNP were found on Chr 1, 2, and 11. These data indicate that genetic background influences vascular function, and the novel QTL identified in this study provide new targets for investigating the underlying mechanisms for variation in vascular function. Supported by NIH grant HL085918 to MPM