Microsomal triglyceride transfer protein polymorphisms and lipoprotein levels in type 2 diabetes.
BACKGROUND
Microsomal triglyceride transfer protein (MTP) regulates the assembly of chylomicrons in the intestine and very-low-density lipoprotein (VLDL) in the liver. Common polymorphisms have been described that do not affect lipoproteins in non-diabetic subjects. Their effect in diabetes has not been described in a Caucasian population.


OBJECTIVE
To investigate the association of these three common polymorphisms with lipoproteins in type 2 diabetes.


METHODS
Eighty-two patients consumed a high-fat test meal. Chylomicron and VLDL apoB48, apoB100, cholesterol, triglycerides and phospholipids were measured fasting, and at 4 and 6 h postprandially. MTP genotyping was performed by PCR-RFLP.


RESULTS
Thirty-three subjects were heterozygous for the -493 G/T substitution. These patients had significantly lower LDL cholesterol (3.0 +/- 0.2 vs. 3.5 +/- 0.1 mmol/l, p < 0.02). In the postprandial period, they had higher levels of apoB48 in the VLDL fraction (4 h, 7.0 +/- 1.4 vs. 2.9 +/- 0.4 microg/ml plasma, p < 0.002; 6 h, 6.4 +/- 1.0 vs. 3.5 +/- 0.5 microg/ml plasma, p < 0.05). In the VLDL fraction there was significantly less cholesterol at 4 and 6 h (p < 0.05). The -400 A/T substitution gave very similar lipoprotein results, but there was significant linkage dysequilibrium between the two polymorphisms. No association was found between the -164 T/C polymorphism and either plasma lipids or the postprandial lipid profile. ApoE genotype was also examined, but did not influence the above results.


CONCLUSIONS
The common -493 G/T MTP polymorphism is associated with changes in VLDL and LDL in Type 2 diabetic patients. The importance of the changes in apoB48-containing small particles requires further investigation. The significantly lower LDL cholesterol suggests that this polymorphism may confer protection against atherosclerosis in type 2 diabetes.
Phillips
C
C
Department of Diabetes and Endocrinology, Trinity College Dublin and The Adelaide and Meath Hospital, Dublin, Ireland.
Mullan
K
K
Owens
D
D
Tomkin
G H
GH
D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D002914:Chylomicrons / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D002352:Carrier Proteins; D002914:Chylomicrons; D008079:Lipoproteins, VLDL; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol