title: Genetic determinants of metabolic syndrome components in the stroke-prone spontaneously hypertensive rat.
abstract: OBJECTIVE
  The metabolic syndrome is a complex multifactorial disease, which results from interactions between genes on multiple chromosomes and environmental factors. Animal models may facilitate genetic analysis of complex phenotypes by allowing complete control of environmental conditions and the ability to produce designer strains.
  
  
  METHODS
  Stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rat strains were used to construct congenic (SP.WKYGla2a), consomic (SP.WKYGlaYw, WKY.SPGlaYs) and double-introgressed (SP.WKYGla2aYw) strains, which were characterized for metabolic syndrome phenotypes (systolic blood pressure, glucose tolerance and lipid profile) after feeding a 60% fructose diet for 14 days.
  
  
  RESULTS
  The Y consomic strain (SP.WKYGlaYw) demonstrated that the WKY Y chromosome significantly lowered triglyceride levels (3.77 +/- 0.60 versus 9.09 +/- 1.47 mmol/l; P < 0.001) and improved glucose tolerance [area under the curve (AUC): 26.93 +/- 0.81 versus 31.47 +/- 0.89; P < 0.05] compared with SHRSP. The chromosome 2 congenic strain (SP.WKYGla2a) exhibited significantly improved glucose tolerance (AUC: 28.19 +/- 1.17 versus 31.47 +/- 0.89; P < 0.05) and lower systolic blood pressure (161.2 +/- 6.2 versus 179.7 +/- 3.9 mmHg; P < 0.05) compared with SHRSP. 2 x 2 factorial ANOVA identified a significant interaction for glucose metabolism (P = 0.004) in the double-introgressed strain (SP.WKYGla2aYw) between chromosome 2 and Y.
  
  
  CONCLUSIONS
  These results identify novel interacting regions on chromosome 2 and the Y chromosome influencing a cluster of metabolic and cardiovascular phenotypes. Translation to clinical studies will facilitate genetic dissection of human metabolic syndrome.
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Strahorn
authors.forename: Delyth
authors.initials: D
authors.lastname: Graham
authors.forename: Fadi J
authors.initials: FJ
authors.lastname: Charchar
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Martin W
authors.initials: MW
authors.lastname: McBride
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D005632:Fructose / Q000008:administration & dosage; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D014998:Y Chromosome / Q000235:genetics
chemical_list: D001786:Blood Glucose; D014280:Triglycerides; D005632:Fructose