TGFB3 displays parent-of-origin effects among central Europeans with nonsyndromic cleft lip and palate.
Mice with a deletion of Tgf-beta3 (-/-) and association studies in humans of different ethnicities support the involvement of TGFB3 in the etiology of orofacial clefts. In this study, we investigated the relevance of TGFB3 in the development of cleft lip and palate (CL/P) among 204 triads of central European origin. Transmission-disequilibrium test (TDT) analysis revealed no significant transmission distortions for each marker alone, and none for any possible haplotypes. However, we found strong evidence for parent-of-origin effects, with lower risk of maternal transmission compared with paternal transmission [I (M) = 0.38; confidence interval (CI): 0.17-0.86] of the risk allele T to an affected offspring at marker rs2300607. This is also expressed in an increased risk of heterozygous children having the T allele inherited from the father (R (P) = 3.47; CI: 1.32-9.11). Our data support the involvement of TGFB3 in the development of oral clefts in patients of central European origin.
Reutter
Heiko
H
Institute of Human Genetics, University of Bonn, Wilhelmstr. 31, 53111, Bonn, Germany. reutter@uni-bonn.de.
Birnbaum
Stefanie
S
Institute of Human Genetics, University of Bonn, Wilhelmstr. 31, 53111, Bonn, Germany.
Mende
Meinhard
M
Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
Lauster
Carola
C
Department of Cleft Lip and Cleft Palate Surgery, Humboldt University of Berlin, Berlin, Germany.
Schmidt
Gül
G
Department of Cleft Lip and Cleft Palate Surgery, Humboldt University of Berlin, Berlin, Germany.
Henschke
Henning
H
Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
Saffar
Mitra
M
Department of Orthodontics, University of Cologne, Cologne, Germany.
Martini
Markus
M
Department of Oral and Maxillo-Facial Surgery, University of Bonn, Bonn, Germany.
Lauster
Roland
R
Molecular Biology, German Arthritis Research Centre, Berlin, Germany.
Schiefke
Franziska
F
Department of Oral and Maxillo-Facial Surgery, University of Leipzig, Leipzig, Germany.
Reich
Rudolf H
RH
Department of Oral and Maxillo-Facial Surgery, University of Bonn, Bonn, Germany.
Braumann
Bert
B
Department of Orthodontics, University of Cologne, Cologne, Germany.
Scheer
Martin
M
Department of Oral and Maxillo-Facial Surgery, University of Cologne, Cologne, Germany.
Knapp
Michael
M
Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
Nöthen
Markus M
MM
Department of Genomics, Life and Brain Centre, University of Bonn, Bonn, Germany.
Kramer
Franz-Josef
FJ
Department of Oral and Maxillo-Facial Surgery, University of Göttingen, Göttingen, Germany.
Mangold
Elisabeth
E
Institute of Human Genetics, University of Bonn, Wilhelmstr. 31, 53111, Bonn, Germany.
D002648:Child; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005060:Europe; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D010159:Palate / Q000002:abnormalities*; D010290:Parents; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome; D053782:Transforming Growth Factor beta3 / Q000235:genetics*
C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3