Genetic control of plasma lipid levels in a cross derived from normoglycaemic Brown Norway and spontaneously diabetic Goto-Kakizaki rats.
OBJECTIVE
Dyslipidaemia is a main component of the insulin resistance syndrome. The inbred Goto-Kakizaki (GK) rat is a model of spontaneous type 2 diabetes and insulin resistance, which has been used to identify diabetes-related susceptibility loci in genetic crosses. The objective of our study was to test the genetic control of lipid metabolism in the GK rat and investigate a possible relationship with known genetic loci regulating glucose homeostasis in this strain.


METHODS
Plasma concentration of triglycerides, phospholipids, total cholesterol, HDL, LDL and VLDL cholesterol were determined in a cohort of 151 hybrids of an F2 cross derived from GK and non-diabetic Brown Norway (BN) rats. Data from the genome-wide scan of the F2 hybrids were used to test for evidence of genetic linkage to the lipid quantitative traits.


RESULTS
We identified statistically significant quantitative trait loci (QTLs) that control the level of plasma phospholipids and triglycerides (chromosome 1), LDL cholesterol (chromosome 3) and total and HDL cholesterol (chromosomes 1 and 5). These QTLs do not coincide with previously identified diabetes susceptibility loci in a similar cross. The significance of lipid QTLs mapped to chromosomes 1 and 5 is strongly influenced by sex.


CONCLUSIONS
We established that several genetic loci control the quantitative variations of plasma lipid variables in a GKxBN cross. They appear to be distinct from known GK diabetes QTLs, indicating that lipid metabolism and traits directly relevant to glucose and insulin regulation are controlled by different gene variants in this strain combination.
Argoud
K
K
The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
Wilder
S P
SP
McAteer
M A
MA
Bihoreau
M T
MT
Ouali
F
F
Woon
P Y
PY
Wallis
R H
RH
Ktorza
A
A
Gauguier
D
D
D000818:Animals; D001786:Blood Glucose / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood / Q000235:genetics; D008297:Male; D010743:Phospholipids / Q000097:blood; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005819:Genetic Markers; D008055:Lipids; D008074:Lipoproteins; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol