Testing reported associations of genetic risk factors for oral clefts in a large Irish study population.
Testing reported associations of genetic risk factors for oral clefts in a large Irish study population.
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测试报告了大型爱尔兰研究人群中口腔裂口的遗传危险因素的关联。
DOI：
10.1002/bdra.20639
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发表时间：
2010-02
影响因子：
--
通讯作者：
Mills, James L.
中科院分区：
文献类型：
--
作者：
Carter, Tonia C.;Molloy, Anne M.;Pangilinan, Faith;Troendle, James F.;Kirke, Peadar N.;Conley, Mary R.;Orr, David J. A.;Earley, Michael;McKiernan, Eamon;Lynn, Ena C.;Doyle, Anne;Scott, John M.;Brody, Lawrence C.;Mills, James L.
提示，但不是结论性的，研究暗示许多遗传变异在口腔唇裂的病因。我们使用了一个大的、种族同质的研究人群来检验报告的非综合征性口腔唇裂与12个基因（CLPTM1、CRISPLD2、FGFR2、GABRB3、GLI2、IRF6、PTCH1、RARA、RYK、SATB2、SUMO1、TGFA）之间的关联是否可以证实。研究了509例伴有或不伴有腭裂（CLP）的唇裂患者、383例单纯腭裂（CP）患者、838例唇裂患者的母亲和719例唇裂患者的父亲以及来自爱尔兰的902例对照者的外显子、剪接位点和保守非编码区31个单核苷酸多态性（snp）。病例对照和基于家庭的统计检验以孤立性唇裂为主要分析对象。在病例对照比较中，PTCH1 A562A的小等位基因（rs2066836）与CLP发生率降低相关（纯合子OR: 0.29, 95% CI: 0.13-0.64），而PTCH1 L1315P的小等位基因（rs357564）与CLP发生率增加相关（杂合子OR: 1.36, 95% CI: 1.07-1.74，纯合子OR: 1.56, 95% CI: 1.09-2.24）。一个SUMO1 SNP的次要等位基因rs3769817位于内含子2，与CP的几率增加相关（杂合子OR: 1.45, 95% CI: 1.06-1.99）。TGFA V159V （rs2166975）的次要等位基因在CP病例中存在传递不平衡（P=0.041）。对于12个基因中的10个，这是迄今为止最大的非综合征性唇裂候选基因研究。研究结果进一步证明PTCH1、SUMO1和TGFA与非综合征性唇裂有关。
Suggestive, but not conclusive, studies implicate many genetic variants in oral cleft etiology. We used a large, ethnically homogenous study population to test whether reported associations between nonsyndromic oral clefts and 12 genes (CLPTM1, CRISPLD2, FGFR2, GABRB3, GLI2, IRF6, PTCH1, RARA, RYK, SATB2, SUMO1, TGFA) could be confirmed. Thirty-one single nucleotide polymorphisms (SNPs) in exons, splice sites, and conserved non-coding regions were studied in 509 patients with cleft lip with or without cleft palate (CLP), 383 with cleft palate only (CP), 838 mothers and 719 fathers of patients with oral clefts, and 902 controls from Ireland. Case-control and family-based statistical tests were performed using isolated oral clefts for the main analyses. In case-control comparisons, the minor allele of PTCH1 A562A (rs2066836) was associated with reduced odds of CLP (OR: 0.29, 95% CI: 0.13–0.64 for homozygotes) whereas the minor allele of PTCH1 L1315P (rs357564) was associated with increased odds of CLP (OR: 1.36, 95% CI: 1.07–1.74 for heterozygotes and OR: 1.56, 95% CI: 1.09–2.24 for homozygotes). The minor allele of one SUMO1 SNP, rs3769817 located in intron 2, was associated with increased odds of CP (OR: 1.45, 95% CI: 1.06–1.99 for heterozygotes). Transmission disequilibrium was observed for the minor allele of TGFA V159V (rs2166975) which was over-transmitted to CP cases (P=0.041). For 10 of the 12 genes, this is the largest candidate gene study of nonsyndromic oral clefts to date. The findings provide further evidence that PTCH1, SUMO1, and TGFA contribute to nonsyndromic oral clefts.
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影响因子：
2
作者：
Genisca, Alicia E.;Frias, Jaime L.;Broussard, Cheryl S.;Honein, Margaret A.;Lammer, Edward J.;Moore, Cynthia A.;Shaw, Gary M.;Murray, Jeffrey C.;Yang, Wei;Rasmussen, Sonja A.
通讯作者：
Rasmussen, Sonja A.
影响因子：
3.5
作者：
Chiquet, Brett T.;Lidral, Andrew C.;Hecht, Jacqueline T.
通讯作者：
Hecht, Jacqueline T.
影响因子：
3.7
作者：
Jugessur A;Shi M;Gjessing HK;Lie RT;Wilcox AJ;Weinberg CR;Christensen K;Boyles AL;Daack-Hirsch S;Trung TN;Bille C;Lidral AC;Murray JC
通讯作者：
Murray JC
影响因子：
30.8
作者：
Birnbaum, Stefanie;Ludwig, Kerstin U.;Mangold, Elisabeth
通讯作者：
Mangold, Elisabeth
影响因子：
3.3
作者：
Briley, GP;Hissong, MA;Lee, DC
通讯作者：
Lee, DC