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

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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.

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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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Authors and Affiliations

  1. Laboratory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan

    Eri Nishihara, Chieko Tsukahara, Satoshi Kunita, Ken-ichi Yagami & Fumihiro Sugiyama

  2. The Jackson Laboratory, 600 Main Street Bar Harbor, Maine, 4609, USA

    Shirng-Wern Tsaih, Sarah Langley, Susan Sheehan, Keith DiPetrillo, Gary A. Churchill & Beverly Paigen

  3. Novartis Institutes for BioMedical Research, East Hanover, New Jersey, 07936, USA

    Keith DiPetrillo

Authors
  1. Eri Nishihara
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  2. Shirng-Wern Tsaih
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  3. Chieko Tsukahara
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  4. Sarah Langley
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  5. Susan Sheehan
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  6. Keith DiPetrillo
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  7. Satoshi Kunita
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  8. Ken-ichi Yagami
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  9. Gary A. Churchill
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  10. Beverly Paigen
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  11. Fumihiro Sugiyama
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Corresponding author

Correspondence to Fumihiro Sugiyama.

Additional information

Eri Nishihara, Shirng-Wern Tsaih, Chieko Tsukahara and Sarah Langley contributed equally to this work.

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Nishihara, E., Tsaih, SW., Tsukahara, C. et al. Quantitative trait loci associated with blood pressure of metabolic syndrome in the progeny of NZO/HILtJ × C3H/HeJ intercrosses. Mamm Genome 18, 573–583 (2007). https://doi.org/10.1007/s00335-007-9033-5

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  • DOI: https://doi.org/10.1007/s00335-007-9033-5

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