Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate
Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate
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Rs7205289 婴儿基因型与腭裂孕妇被动吸烟相互作用的生物学和流行病学证据
DOI：
10.1002/ajmg.a.34254
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发表时间：
2011-12-01
影响因子：
2
通讯作者：
Shi, Bing
中科院分区：
文献类型：
--
作者：
Li, Ling;Zhu, Gui-quan;Shi, Bing
位于microRNA-140基因中的非编码SNP rs7205289与腭裂风险相关。MiR-140在体内调节斑马鱼腭发育，其表达水平因体外环境烟雾暴露而降低。因此，我们试图研究rs7205289的A等位基因和妊娠早期母亲吸烟暴露是否可能通过调节microRNA-140而增加腭裂风险。我们使用原位杂交技术来探索microRNA-140的表达模式。利用荧光素酶报告系统和Western blot对microRNA-140的靶标进行验证。用microRNA-140表达载体转染小鼠腭间充质细胞（MPMC），或用香烟烟雾提取物处理。此外，我们对169例非综合征性腭裂患者和306例未受影响的对照组进行了以医院为基础的病例对照研究。我们证实了microRNA-140在小鼠胚胎12 - 15天的腭架上表达。Pdgfra是MPMC中microRNA-140的靶标。当这些细胞用次要等位基因载体转染或暴露于香烟烟雾提取物时，它们显示出microRNA-140的表达降低。流行病学分析表明，CA/AA基因型的婴儿和孕期暴露于母亲被动吸烟的婴儿在腭裂风险中存在协同相互作用的证据。我们得出结论，CA/AA基因型rs7205289的婴儿和母亲在妊娠早期被动吸烟可能通过降低腭发育过程中的microRNA-140协同增加腭裂风险。(C) 2011 Wiley期刊公司
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 casecontrol 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. Pdgfra 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.