A common functional exon polymorphism in the microsomal triglyceride transfer protein gene is associated with type 2 diabetes, impaired glucose metabolism and insulin levels.
The microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apolipoprotein B-containing lipoproteins. Emerging evidence has indicated that the functional MTP exon polymorphism I128T is associated with dyslipidemia and other traits of the insulin-resistance syndrome, and the T128 variant seems to confer a reduced stability of MTP, resulting in reduced binding of LDL particles. The aim of the study was to elucidate the association of this MTP polymorphism with parameters of postprandial metabolism. A total of 716 male subjects from a postprandially characterized cohort (MICK) and a nested case-control study (EPIC) of 190 incident type 2 diabetes cases and 380 sex- or age-matched controls were genotyped for the I128T exon polymorphism. In comparison to homozygote subjects of the wild allele, carriers of the less common allele of the MTP T128 genotype showed significantly lower postprandial insulin levels (P=0.017), lower diastolic blood pressure (P=0.049) and had a lower prevalence of impaired glucose metabolism and diabetes type 2 (P=0.03) in the MICK. Consistent with this, we found a lower incidence of type 2 diabetes in male subjects of the nested case-control study in the T128 genotype (P=0.007). These results suggest that the rare allele of the MTP I128T polymorphism may be protective against impaired glucose tolerance, type 2 diabetes and other parameters of the metabolic syndrome.
Rubin
Diana
D
Institute of Physiology and Biochemistry of Nutrition, Federal Research Center of Nutrition and Food, Hermann-Weigmann-Str. 1, 24103, Kiel, Germany.|Department of General Internal Medicine, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Helwig
Ulf
U
Institute of Physiology and Biochemistry of Nutrition, Federal Research Center of Nutrition and Food, Hermann-Weigmann-Str. 1, 24103, Kiel, Germany.|Department of General Internal Medicine, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Pfeuffer
Maria
M
Institute of Physiology and Biochemistry of Nutrition, Federal Research Center of Nutrition and Food, Hermann-Weigmann-Str. 1, 24103, Kiel, Germany.
Schreiber
Stefan
S
Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany.
Boeing
Heiner
H
Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany.
Fisher
Eva
E
Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany.
Pfeiffer
Andreas
A
Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam, Germany.
Freitag-Wolf
Sandra
S
Institute of Medical Informatics and Statistics, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Foelsch
Ulrich R
UR
Department of General Internal Medicine, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Doering
Frank
F
Research Group Molecular Nutrition, Christian-Albrechts University, Kiel, Germany.
Schrezenmeir
Juergen
J
Institute of Physiology and Biochemistry of Nutrition, Federal Research Center of Nutrition and Food, Hermann-Weigmann-Str. 1, 24103, Kiel, Germany. schrezenmeir@bafm.de.
D000368:Aged; D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D005858:Germany; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; C106092:microsomal triglyceride transfer protein