Analysis of interactions between genetic variants of BMP4 and environmental factors with nonsyndromic cleft lip with or without cleft palate susceptibility.
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.
Jianyan
L
L
Nan Ning Center for Disease Control & Prevention, Nanning, Guangxi, China.
Zeqiang
G
G
Yongjuan
C
C
Kaihong
D
D
Bing
D
D
Rongsheng
L
L
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003596:Cytosine; D019587:Dietary Supplements; D004198:Disease Susceptibility; D004781:Environmental Exposure; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D018811:Maternal Exposure; D018812:Paternal Exposure; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012907:Smoking / Q000235:genetics; D013941:Thymine; D014028:Tobacco Smoke Pollution; D014815:Vitamins / Q000627:therapeutic use; D055815:Young Adult
C525809:BMP4 protein, human; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D014028:Tobacco Smoke Pollution; D014815:Vitamins; D003596:Cytosine; D013941:Thymine