Abnormal Igf2 gene in Prague hereditary hypertriglyceridemic rats: its relation to blood pressure and plasma lipids
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Prague hypertriglyceridemic (HTG) rats represent a suitable model of metabolic syndrome. We have established the set of F2 hybrids derived from HTG and Lewis progenitors to investigate the relationship between respective polymorphism(s) of Igf2 gene and blood pressure (BP) or other cardiovascular phenotypes. HTG rats had elevated systolic BP and plasma triglycerides but lower plasma cholesterol compared to Lewis rats of both genders. In males, there was higher mean arterial pressure, diastolic BP and relative heart weight in HTG than in Lewis rats. The results obtained in the total population of F2 hybrids indicated strong segregation of Igf2 genotype with plasma triglycerides. There was no segregation of Igf2 genotype with any BP component except BP changes occurring after the blockade of either renin–angiotensin system (RAS) or NO synthase. When F2 population was analyzed according to gender, male F2 progeny homozygous for HTG Igf2 allele had significantly higher plasma triglycerides and greater BP changes after NO synthase blockade than those homozygous for Lewis allele. On the contrary, male F2 progeny homozygous for HTG Igf2 allele had significantly lower plasma cholesterol and smaller BP changes after RAS blockade. PCR analysis of Igf2 gene by using of microsatelite D1Mgh22 has shown polymorphism between HTG and Lewis rats. Sequence analysis of cDNA revealed insertion of 14 nucleotides in HTG gene. In conclusion, polymorphism in Igf2 gene may be responsible for differences in lipid metabolism between HTG and Lewis rats. It remains to determine how these abnormalities could be involved in BP regulation by particular vasoactive systems.
KeywordsPlasma cholesterol Triglycerides Polymorphism Genetic determinants Hypertension F2 hybrids Metabolic syndrome
This work was supported by AV0Z 5110509, Centre for Cardiovascular Research (1M0510), and GA CR grant 305/08/0139.
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