title: TGF-beta1 gene mutations in insulin-dependent diabetes mellitus and diabetic nephropathy.
abstract: PCR assays were established for easy and fast analysis of two transforming growth factor-beta1 (TGF-beta1) gene mutations, a C to T transition at position 76 in exon 5 resulting in a change from threonine to isoleucine in position 263 (Thr263Ile) of the propeptide and a deletion of a C in the intron sequence eight bases prior to exon 5 (713-8delC). These mutations were evaluated in insulin-dependent diabetes mellitus (IDDM) patients (n = 137) and control subjects (n = 105) and in IDDM patients with (n = 170) and without (n = 99) nephropathy. After evaluating intra- and interindividual variation in TGF-beta1 expression levels, the TGF-beta1 mRNA level in phorbol 12-myristate-13-acetate-stimulated (1 ng/ml) lymphocytes from individuals with different TGF-beta1 genotypes was also studied. No association of the two TGF-beta1 sequence variations with IDDM in general was found. However, a weak but significant association of the Thr263Ile mutation with diabetic nephropathy was found (P = 0.03). No correlation between TGF-beta1 transcription level and genotype of any of the two studied polymorphisms was found. However, significant interindividual differences in TGF-beta1 mRNA levels were observed between the tested individuals (P < 0.0001) compatible with a genetic control mechanism of TGF-beta1 synthesis at the mRNA level.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Pociot
authors.forename: P M
authors.initials: PM
authors.lastname: Hansen
authors.forename: A E
authors.initials: AE
authors.lastname: Karlsen
authors.forename: B L
authors.initials: BL
authors.lastname: Langdahl
authors.forename: J
authors.initials: J
authors.lastname: Johannesen
authors.forename: J
authors.initials: J
authors.lastname: Nerup
mesh_terms: D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D007438:Introns / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D016212:Transforming Growth Factor beta; D013755:Tetradecanoylphorbol Acetate