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American Journal of Epidemiology Advance Access published online on February 22, 2006
American Journal of Epidemiology, doi:10.1093/aje/kwj103
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.
Received October 8, 2003
Accepted December 13, 2005

HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEW

Association between the Transforming Growth Factor Alpha Gene and Nonsyndromic Oral Clefts: A HuGE Review

Alexandre R. Vieira 1 *

1 From the Department of Oral Medicine and Pathology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA

* To whom correspondence should be addressed.
Alexandre R. Vieira, E-mail: arv11{at}dental.pitt.edu


  Abstract

Transforming growth factor alpha (TGFA) is a well-characterized mammalian growth factor. Since the first report of an association between DNA sequence variants at the TGFA genetic locus and nonsyndromic oral clefts, 47 studies have been carried out, producing conflicting results. In this review, the author synthesizes findings from published reports on the association between the TGFA gene and clefting in humans. Bias, lack of statistical power, and genuine population diversity can explain the diverse results. In the aggregate, TGFA is probably a genetic modifier of clefting in humans, which is consistent with the oligogenic model suggested for nonsyndromic oral clefts.

Keywords: cleft lip; cleft palate; epidemiology; genetics; TGFA; transforming growth factor alpha.
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