| First Author | Li L | Year | 2011 |
| Journal | Am J Med Genet A | Volume | 155A |
| Issue | 12 | Pages | 2940-8 |
| PubMed ID | 22012839 | Mgi Jnum | J:178144 |
| Mgi Id | MGI:5297614 | Doi | 10.1002/ajmg.a.34254 |
| Citation | Li L, et al. (2011) Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate. Am J Med Genet A 155(12):2940-8 |
| abstractText | 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. Pdgfralpha 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. (c) 2011 Wiley Periodicals, Inc. |
