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Mammalian Genome

, Volume 18, Issue 8, pp 573–583 | Cite as

Quantitative trait loci associated with blood pressure of metabolic syndrome in the progeny of NZO/HILtJ × C3H/HeJ intercrosses

  • Eri Nishihara
  • Shirng-Wern Tsaih
  • Chieko Tsukahara
  • Sarah Langley
  • Susan Sheehan
  • Keith DiPetrillo
  • Satoshi Kunita
  • Ken-ichi Yagami
  • Gary A. Churchill
  • Beverly Paigen
  • Fumihiro Sugiyama
Article

Abstract

In a previous study in 15 inbred mouse strains, we found highest and lowest systolic blood pressures in NZO/HILtJ mice (metabolic syndrome) and C3H/HeJ mice (common lean strain), respectively. To identify the loci involved in hypertension in metabolic syndrome, we performed quantitative trait locus (QTL) analysis for blood pressure with direction of cross as a covariate in segregating F2 males derived from NZO/HILtJ and C3H/HeJ mice. We detected three suggestive main-effect QTLs affecting systolic and diastolic blood pressures (SBP and DBP). We analyzed the first principle component (PC1) generated from SBP and DBP to investigate blood pressure. In addition to all the suggestive QTLs (Chrs 1, 3, and 8) in SBP and DBP, one suggestive QTL on Chr 4 was found in PC1 in the main scan. Simultaneous search identified two significant epistatic locus pairs (Chrs 1 and 4, Chrs 4 and 8) for PC1. Multiple regression analysis revealed three blood pressure QTLs (Bpq10, 100 cM on Chr 1; Bpq11, 6 cM on Chr 4; Bpq12, 29 cM on Chr 8) accounting for 29.4% of blood pressure variance. These were epistatic interaction QTLs constructing a small network centered on Chr 4, suggesting the importance of genetic interaction for development of hypertension. The blood pressure QTLs on Chrs 1, 4, and 8 were detected repeatedly in multiple studies using common inbred nonobese mouse strains, implying substantial QTL independent of development of obesity and insulin resistance. These results enhance our understanding of complicated genetic factors of hypertension in metabolic diseases.

Keywords

Quantitative Trait Locus Diastolic Blood Pressure Single Nucleotide Polymorphic Quantitative Trait Locus Analysis Epistatic Interaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sport, Science and Technology of Japan (to FS, KS, and KY).

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Eri Nishihara
    • 1
  • Shirng-Wern Tsaih
    • 2
  • Chieko Tsukahara
    • 1
  • Sarah Langley
    • 2
  • Susan Sheehan
    • 2
  • Keith DiPetrillo
    • 2
    • 3
  • Satoshi Kunita
    • 1
  • Ken-ichi Yagami
    • 1
  • Gary A. Churchill
    • 2
  • Beverly Paigen
    • 2
  • Fumihiro Sugiyama
    • 1
  1. 1.Laboratory Animal Resource CenterUniversity of TsukubaTsukubaJapan
  2. 2.The Jackson LaboratoryMaineUSA
  3. 3.Novartis Institutes for BioMedical ResearchNew JerseyUSA

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