Q J Med 2004; 97: 211-218
QJM vol. 97 no. 4 (c) Association of Physicians 2004; all rights reserved.
Microsomal triglyceride transfer protein polymorphisms and lipoprotein levels in type 2 diabetes
From the Department of Diabetes and Endocrinology, Trinity College Dublin and The Adelaide and Meath Hospital, Dublin, Ireland
Received 14 October 2003 and in revised form 19 January 2004
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.
Aim: 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 µg/ml plasma, p < 0.002; 6 h, 6.4 ± 1.0 vs. 3.5 ± 0.5 µg/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.
Discussion: 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.
Address correspondence to Professor G.H. Tomkin, 1 Fitzwilliam Square, Dublin 2, Ireland. e-mail gtomkin{at}rcsi.ie
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