title: A common functional exon polymorphism in the microsomal triglyceride transfer protein gene is associated with type 2 diabetes, impaired glucose metabolism and insulin levels.
abstract: 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.
authors.affiliation: 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.
authors.forename: Diana
authors.initials: D
authors.lastname: Rubin
authors.affiliation: 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.
authors.forename: Ulf
authors.initials: U
authors.lastname: Helwig
authors.affiliation: Institute of Physiology and Biochemistry of Nutrition, Federal Research Center of Nutrition and Food, Hermann-Weigmann-Str. 1, 24103, Kiel, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Pfeuffer
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfeiffer
authors.affiliation: Institute of Medical Informatics and Statistics, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Freitag-Wolf
authors.affiliation: Department of General Internal Medicine, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Ulrich R
authors.initials: UR
authors.lastname: Foelsch
authors.affiliation: Research Group Molecular Nutrition, Christian-Albrechts University, Kiel, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Doering
authors.affiliation: Institute of Physiology and Biochemistry of Nutrition, Federal Research Center of Nutrition and Food, Hermann-Weigmann-Str. 1, 24103, Kiel, Germany. schrezenmeir@bafm.de.
authors.forename: Juergen
authors.initials: J
authors.lastname: Schrezenmeir
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; C106092:microsomal triglyceride transfer protein