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Genetic linkage of hyperglycemia and dyslipidemia in an intercross between BALB/cJ and SM/J Apoe-deficient mouse strains.

Wang Q, Grainger AT, Manichaikul A, Farber E, Onengut-Gumuscu S, Shi W - BMC Genet. (2015)

Bottom Line: One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels.Bglu17 coincided with a significant QTL for HDL (high-density lipoprotein) and a suggestive QTL for non-HDL cholesterol levels.We have identified multiple QTLs for fasting glucose and lipid levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology & Medical Imaging, University of Virginia, Snyder Bldg Rm 266, 480 Ray C. Hunt Dr., P.O. Box 801339, Fontaine Research Park, Charlottesville, VA, 22908, USA. qw3q@Virginia.EDU.

ABSTRACT

Background: Individuals with dyslipidemia often develop type 2 diabetes, and diabetic patients often have dyslipidemia. It remains to be determined whether there are genetic connections between the 2 disorders.

Methods: A female F2 cohort, generated from BALB/cJ (BALB) and SM/J (SM) Apoe-deficient (Apoe(-/-)) strains, was started on a Western diet at 6 weeks of age and maintained on the diet for 12 weeks. Fasting plasma glucose and lipid levels were measured before and after 12 weeks of Western diet. 144 genetic markers across the entire genome were used for quantitative trait locus (QTL) analysis.

Results: One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels. The suggestive QTL near the proximal end of chromosome 9 (2.4 cM, LOD: 3.12) was replicated at both time points and named Bglu16. Bglu17 coincided with a significant QTL for HDL (high-density lipoprotein) and a suggestive QTL for non-HDL cholesterol levels. Plasma glucose levels were inversely correlated with HDL but positively correlated with non-HDL cholesterol levels in F2 mice on either chow or Western diet. A significant correlation between fasting glucose and triglyceride levels was also observed on the Western diet. Haplotype analysis revealed that "lipid genes" Sik3, Apoa1, and Apoc3 were probable candidates for Bglu17.

Conclusions: We have identified multiple QTLs for fasting glucose and lipid levels. The colocalization of QTLs for both phenotypes and the sharing of potential candidate genes demonstrate genetic connections between dyslipidemia and type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus

Correlations of fasting plasma glucose levels with plasma levels of HDL, non-HDL cholesterol and triglyceride in the F2 population fed a chow (top row: a, b, c) or Western diet (bottom row: d, e, f). Each point represents values of an individual F2 mouse. The correlation coefficient (R) and significance (P) are shown
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Fig7: Correlations of fasting plasma glucose levels with plasma levels of HDL, non-HDL cholesterol and triglyceride in the F2 population fed a chow (top row: a, b, c) or Western diet (bottom row: d, e, f). Each point represents values of an individual F2 mouse. The correlation coefficient (R) and significance (P) are shown

Mentions: The correlations of fasting glucose levels with plasma levels of HDL, non-HDL cholesterol, or triglyceride were analyzed with the F2 population (Fig. 7). A significant inverse correlation between fasting glucose and HDL cholesterol levels was observed when the mice were fed a chow (R = −0.220; P = 8.1E-4) or Western diet (R = −0.257; P = 8.5E-5). F2 mice with higher HDL cholesterol levels had lower fasting glucose levels. Conversely, significant positive correlations between fasting glucose and non-HDL cholesterol levels were observed when mice were fed either chow (R = 0.194; P = 3.31E-3) or Western diet (R = 0.558; P = 4.7E-20). F2 mice with higher non-HDL cholesterol levels also had higher fasting glucose levels, especially on the Western diet. A significant positive correlation between plasma levels of fasting glucose and triglyceride was observed when mice were fed the Western diet (R = 0.377; P = 3.9E-9) but not the chow diet (R = 0.065; P = 0.330).Fig. 7


Genetic linkage of hyperglycemia and dyslipidemia in an intercross between BALB/cJ and SM/J Apoe-deficient mouse strains.

Wang Q, Grainger AT, Manichaikul A, Farber E, Onengut-Gumuscu S, Shi W - BMC Genet. (2015)

Correlations of fasting plasma glucose levels with plasma levels of HDL, non-HDL cholesterol and triglyceride in the F2 population fed a chow (top row: a, b, c) or Western diet (bottom row: d, e, f). Each point represents values of an individual F2 mouse. The correlation coefficient (R) and significance (P) are shown
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4641414&req=5

Fig7: Correlations of fasting plasma glucose levels with plasma levels of HDL, non-HDL cholesterol and triglyceride in the F2 population fed a chow (top row: a, b, c) or Western diet (bottom row: d, e, f). Each point represents values of an individual F2 mouse. The correlation coefficient (R) and significance (P) are shown
Mentions: The correlations of fasting glucose levels with plasma levels of HDL, non-HDL cholesterol, or triglyceride were analyzed with the F2 population (Fig. 7). A significant inverse correlation between fasting glucose and HDL cholesterol levels was observed when the mice were fed a chow (R = −0.220; P = 8.1E-4) or Western diet (R = −0.257; P = 8.5E-5). F2 mice with higher HDL cholesterol levels had lower fasting glucose levels. Conversely, significant positive correlations between fasting glucose and non-HDL cholesterol levels were observed when mice were fed either chow (R = 0.194; P = 3.31E-3) or Western diet (R = 0.558; P = 4.7E-20). F2 mice with higher non-HDL cholesterol levels also had higher fasting glucose levels, especially on the Western diet. A significant positive correlation between plasma levels of fasting glucose and triglyceride was observed when mice were fed the Western diet (R = 0.377; P = 3.9E-9) but not the chow diet (R = 0.065; P = 0.330).Fig. 7

Bottom Line: One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels.Bglu17 coincided with a significant QTL for HDL (high-density lipoprotein) and a suggestive QTL for non-HDL cholesterol levels.We have identified multiple QTLs for fasting glucose and lipid levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology & Medical Imaging, University of Virginia, Snyder Bldg Rm 266, 480 Ray C. Hunt Dr., P.O. Box 801339, Fontaine Research Park, Charlottesville, VA, 22908, USA. qw3q@Virginia.EDU.

ABSTRACT

Background: Individuals with dyslipidemia often develop type 2 diabetes, and diabetic patients often have dyslipidemia. It remains to be determined whether there are genetic connections between the 2 disorders.

Methods: A female F2 cohort, generated from BALB/cJ (BALB) and SM/J (SM) Apoe-deficient (Apoe(-/-)) strains, was started on a Western diet at 6 weeks of age and maintained on the diet for 12 weeks. Fasting plasma glucose and lipid levels were measured before and after 12 weeks of Western diet. 144 genetic markers across the entire genome were used for quantitative trait locus (QTL) analysis.

Results: One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels. The suggestive QTL near the proximal end of chromosome 9 (2.4 cM, LOD: 3.12) was replicated at both time points and named Bglu16. Bglu17 coincided with a significant QTL for HDL (high-density lipoprotein) and a suggestive QTL for non-HDL cholesterol levels. Plasma glucose levels were inversely correlated with HDL but positively correlated with non-HDL cholesterol levels in F2 mice on either chow or Western diet. A significant correlation between fasting glucose and triglyceride levels was also observed on the Western diet. Haplotype analysis revealed that "lipid genes" Sik3, Apoa1, and Apoc3 were probable candidates for Bglu17.

Conclusions: We have identified multiple QTLs for fasting glucose and lipid levels. The colocalization of QTLs for both phenotypes and the sharing of potential candidate genes demonstrate genetic connections between dyslipidemia and type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus