Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate.
The noncoding SNP rs7205289, located in the microRNA-140 gene has been associated with cleft palate risk. MiR-140 was found to regulate zebrafish palatal development in vivo and its expression level be reduced by environmental smoke exposure in vitro. Therefore, we sought to investigate whether the A allele of rs7205289 and maternal smoke exposure during the first trimester might contribute to cleft palate risk by regulating microRNA-140. We used in situ hybridization to explore the microRNA-140 expression pattern. A luciferase reporting system and Western blot were used to validate the target of microRNA-140. Mouse palatal mesenchymal cells (MPMC) were transfected with microRNA-140 expression vectors, or treated with cigarette smoke extract. In addition, we performed a hospital-based case-control study in 169 patients with nonsyndromic cleft palate and 306 unaffected controls. We demonstrated microRNA-140 expression in mouse palatal shelves from embryonic days 12 to 15. Pdgfrα was the target of microRNA-140 in MPMC. When these cells were transfected with the minor allele vector or exposed to cigarette smoke extract, they showed a decrease in microRNA-140 expression. Epidemiological analyses showed that infants with CA/AA genotypes and exposed to maternal passive smoking during pregnancy had evidence of synergistic interaction in contributing to cleft palate risk. We concluded that infants with CA/AA genotypes at rs7205289 and maternal passive smoking during the first trimester may synergistically contribute to cleft palate risk by decreasing microRNA-140 during palatal development.
State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China.
Ling
L
Li
Gui-Quan
GQ
Zhu
Tian
T
Meng
Jia-Yu
JY
Shi
Jun
J
Wu
Xue
X
Xu
Bing
B
Shi
D000483:Alleles; D000818:Animals; D002972:Cleft Palate / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D018811:Maternal Exposure; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014028:Tobacco Smoke Pollution
C547828:MIRN140 microRNA, mouse; D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D014028:Tobacco Smoke Pollution; D020796:Receptor, Platelet-Derived Growth Factor alpha