title: Analysis of polymorphic TGFB1 codons 10, 25, and 263 in a German patient group with non-syndromic cleft lip, alveolus, and palate compared with healthy adults.
abstract: BACKGROUND
  Clefts of the lip, alveolus, and palate (CLPs) rank among the most frequent and significant congenital malformations. Leu10Pro and Arg25Pro polymorphisms in the precursor region and Thr263Ile polymorphism in the prodomain of the transforming growth factor beta1 (TGF-beta1) gene have proved to be crucial to predisposition of several disorders.
  
  
  METHODS
  In this study, polymorphism analysis was performed by real-time polymerase chain reaction (LightCycler) and TGF-beta1 levels determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Only 2/60 Caucasian non-syndromic patients with CLP (3.3%) carried the Arg25Pro and another 2/60 patients (3.3%) the Thr263Ile genotypes, whereas, in a control group of 60 healthy Caucasian blood donors, these heterozygous genotypes were more frequent 16.7% having Arg25Pro (10/60; p < 0.035) and 10,0% having Thr263Ile (6/60), respectively. TGF-beta1 levels in platelet-poor plasma of heterozygous Arg25Pro individuals were lower than those of homozygous members (Arg25Arg) in the latter group, but this discrepancy narrowly failed to be significant. Although polymorphisms in codon 10 and 25 were associated with each other, no difference was found between patients and controls concerning the Leu10Pro polymorphism.
  
  
  CONCLUSIONS
  The genetic differences in codons 25 and 263 suggest that TGF-beta1 could play an important role in occurrence of CLP, however, functional experiments will be required to confirm the mechanisms of disturbed development.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany. cstoll@ukaachen.de
authors.forename: Christian
authors.initials: C
authors.lastname: Stoll
authors.forename: Senait
authors.initials: S
authors.lastname: Mengsteab
authors.forename: Doris
authors.initials: D
authors.lastname: Stoll
authors.forename: Dieter
authors.initials: D
authors.lastname: Riediger
authors.forename: Axel M
authors.initials: AM
authors.lastname: Gressner
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
mesh_terms: D000293:Adolescent; D000328:Adult; D000539:Alveolar Process / Q000002:abnormalities / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000097:blood / Q000235:genetics / Q000473:pathology; D002972:Cleft Palate / Q000097:blood / Q000235:genetics / Q000473:pathology; D003062:Codon / Q000235:genetics*; D000013:Congenital Abnormalities / Q000097:blood / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D005858:Germany; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
chemical_list: D003062:Codon; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D004247:DNA