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Mapping and Congenic Dissection of Genetic Loci Contributing to Hyperglycemia and Dyslipidemia in Mice

BACKGROUND: Patients with dyslipidemia have an increased risk of developing type 2 diabetes, and diabetic patients often have dyslipidemia. Potential genetic connections of fasting plasma glucose with plasma lipid profile were evaluated using hyperlipidemic mice. METHODS: 225 male F(2) mice were gen...

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Detalles Bibliográficos
Autores principales: Shi, Weibin, Wang, Qian, Choi, Wonseok, Li, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747551/
https://www.ncbi.nlm.nih.gov/pubmed/26859786
http://dx.doi.org/10.1371/journal.pone.0148462
Descripción
Sumario:BACKGROUND: Patients with dyslipidemia have an increased risk of developing type 2 diabetes, and diabetic patients often have dyslipidemia. Potential genetic connections of fasting plasma glucose with plasma lipid profile were evaluated using hyperlipidemic mice. METHODS: 225 male F(2) mice were generated from BALB/cJ (BALB) and SM/J(SM) Apoe-deficient (Apoe(−/−)) mice and fed a Western diet for 5 weeks. Fasting plasma glucose and lipid levels of F(2) mice were measured before and after 5 weeks of Western diet and quantitative trait locus (QTL) analysis was performed using data collected from these two time points. 144 SNP(single nucleotide polymorphism) markers across the entire genome were typed. RESULTS: One major QTL (logarithm of odds ratio (LOD): 6.46) peaked at 12.7 cM on chromosome 9,Bglu16, and 3 suggestive QTLs on chromosomes 15, 18 and X were identified for fasting glucose, and over 10 loci identified for lipid traits. Bglu16 was adjacent to a major QTL, Hdlq17, for high-density lipoprotein (HDL) cholesterol (LOD: 6.31, peak: 19.1 cM). A congenic strain with a donor chromosomal region harboring Bglu16 and Hdlq17 on the Apoe(−/−) background showed elevations in plasma glucose and HDL levels. Fasting glucose levels were significantly correlated with non-HDL cholesterol and triglyceride levels, especially on the Western diet, but only marginally correlated with HDL levels in F(2) mice. CONCLUSIONS: We have demonstrated a correlative relationship between fasting glucose and plasma lipids in a segregating F(2) population under hyperlipidemic conditions, and this correlation is partially due to genetic linkage between the two disorders.