Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate.

Abstract

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.

• Authors: Ling Li, Gui-Quan Zhu, Tian Meng, Jia-Yu Shi, Jun Wu, Xue Xu, Bing Shi
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 155A Issue 12 Pg. 2940-8 (Dec 2011) ISSN: 1552-4833 [Electronic] United States
• PMID: 22012839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• MIRN140 microRNA, mouse
• MicroRNAs
• Mirn140 microRNA, human
• Tobacco Smoke Pollution
• Receptor, Platelet-Derived Growth Factor alpha

Topics

• Alleles
• Animals
• Cleft Palate (epidemiology, genetics)
• Female
• Gene Expression Regulation, Developmental
• Gene-Environment Interaction
• Genotype
• Humans
• Infant
• Male
• Maternal Exposure
• Mesenchymal Stem Cells (metabolism)
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Polymorphism, Single Nucleotide
• Pregnancy
• Receptor, Platelet-Derived Growth Factor alpha (genetics)
• Risk Factors
• Surveys and Questionnaires
• Tobacco Smoke Pollution