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Int J Oral Maxillofac Surg. 2010 Jan;39(1):50-6. doi: 10.1016/j.ijom.2009.10.010. Epub 2009 Nov 14.

Analysis of interactions between genetic variants of BMP4 and environmental factors with nonsyndromic cleft lip with or without cleft palate susceptibility.

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Nan Ning Center for Disease Control & Prevention, Nanning, Guangxi, China.


A hospital-based case-control study was conducted to identify interactions between the 538(T-->C) polymorphic site of bone morphogenetic protein 4 gene (BMP4T538C) and exposures in pregnancy with nonsyndromic cleft lip, with or without cleft palate (nsCL/P). Associations between offspring polymorphism of BMP4T538C, paternal smoking, paternal high-risk drinking, maternal passive smoking, and maternal multivitamin supplement with nsCL/P were analyzed by logistic regression analysis. BMP4T538C polymorphism, maternal passive smoking exposures and maternal multivitamin use were associated with the risk of nsCL/P but paternal smoking and paternal high-risk drinking were not. Gene-environment interactions were analyzed using the multifactor dimensionality reduction (MDR) method. The two-factor model including maternal passive smoking and BMP4T538C, was the best for predicting nsCL/P risk with a maximum cross-validation consistency (10/10) and a maximum average testing accuracy(0.605; P<0.0001). The findings suggested that: BMP4T538C could be used as a genetic susceptibility marker for nsCL/P; maternal passive smoking exposure is a risk factor for nsCL/P; maternal multivitamin supplements are a protective factor; the synergistic effect of BMP4T538C and maternal passive smoking could provide a new tool for identifying individuals at high risk of nsCL/P, and provides additional evidence that nsCL/P is determined by genetic and environmental factors.

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