Quantitative trait loci associated with blood pressure of metabolic syndrome in the progeny of NZO/HILtJxC3H/HeJ intercrosses.
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.
Nishihara
Eri
E
Laboratory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
Tsaih
Shirng-Wern
SW
Tsukahara
Chieko
C
Langley
Sarah
S
Sheehan
Susan
S
DiPetrillo
Keith
K
Kunita
Satoshi
S
Yagami
Ken-ichi
K
Churchill
Gary A
GA
Paigen
Beverly
B
Sugiyama
Fumihiro
F
D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D003433:Crosses, Genetic; D005260:Female; D008126:Lod Score; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics*; D008815:Mice, Inbred Strains; D025341:Principal Component Analysis; D040641:Quantitative Trait Loci