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

Authors

  • Ling Li,

    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
    2. Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China
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  • Gui-quan Zhu,

    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
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  • Tian Meng,

    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
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  • Jia-yu Shi,

    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
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  • Jun Wu,

    1. Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China
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  • Xue Xu,

    1. Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China
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  • Bing Shi

    Corresponding author
    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
    2. Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China
    • Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, No. 14, Section 3, RenMinNan Road, Chengdu, PR China.
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  • How to Cite this Article: Li L, Zhu G-q, Meng T, Shi J-y, Wu J, Xu X, Shi B. 2011. Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate. Am J Med Genet Part A 155: 2940–2948.

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. © 2011 Wiley Periodicals, Inc.

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