Nonsyndromic Cleft Lip with or without Cleft Palate in Arab Populations: Genetic Analysis of 15 Risk Loci in a Novel Case-Control Sample Recruited in Yemen

被引:22
作者
Aldhorae, Khalid Ahmed [1 ]
Boehmer, Anne C. [2 ,3 ]
Ludwig, Kerstin U. [2 ,3 ]
Esmail, Ahlam Hibatulla Ali [4 ]
Al-Hebshi, Nezar Noor [5 ]
Lippke, Baerbel [2 ,3 ]
Goelz, Lina [6 ]
Noethen, Markus M. [2 ,3 ]
Daratsianos, Nikolaos [6 ]
Knapp, Michael [7 ]
Jaeger, Andreas [6 ]
Mangold, Elisabeth [2 ]
机构
[1] Thamar Univ, Coll Dent, Dept Orthodont, Thamar, Yemen
[2] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany
[3] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany
[4] Univ Aden, Coll Dent, Cleft Lip & Palate Ctr, Aden, Yemen
[5] Univ Sci & Technol, Fac Med Sci, Mol Res Lab, Sanaa, Yemen
[6] Univ Bonn, Dept Orthodont, D-53127 Bonn, Germany
[7] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53127 Bonn, Germany
关键词
nonsyndromic cleft lip with or without cleft palate; genetic loci; Arab population; single nucleotide polymorphism; orofacial cleft; replication study; SUSCEPTIBILITY LOCUS; GENOME-WIDE; CHROMOSOME; 8Q24; ASSOCIATION; VARIANTS; REVEALS; IRF6; FOXE1; TRIO; VAX1;
D O I
10.1002/bdra.23221
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
BackgroundNonsyndromic orofacial clefting (nsOFC) is among the most common of all congenital disorders and has a genetically complex etiology. Based on embryological and epidemiological data, the phenotype can be differentiated into nonsyndromic cleft lip with or without cleft palate (nsCL/P) and nonsyndromic cleft palate only, with nsCL/P being the most frequent form. Recent genetic research, predominantly performed in populations from Europe and Asia, has identified numerous genetic susceptibility loci for nsCL/P. As only few data are available concerning genetic susceptibility to nsCL/P in Arab populations, we investigated a newly recruited nsOFC sample from Yemen. MethodsFor each of the 15 currently known nsCL/P risk loci, the top single-nucleotide polymorphism (plus nine back-up variants) were genotyped in 242 nsCL/P cases and 420 healthy controls. ResultsSingle-marker association analysis revealed significant associations for four loci (8q24, 9q22, 10q25, 13q31). The strongest association was for the European high risk locus at 8q24 (P-corrected=5.09 x 10(-4); heterozygous odds ratio=1.74 (1.22-2.47), homozygous odds ratio=2.47 (1.55-3.93). Five additional loci (1q32.2, 3q12, 8q21, 17q22, 20q12) showed nominal significance that did not withstand correction for multiple testing. Although the six remaining loci (1p22, 1p36, 2p21, 3p11, 15q22, 17p13) failed to reach nominal significance, the risk alleles were in the same direction as in the discovery studies. ConclusionThe results suggest that four of the 15 analyzed nsCL/P risk loci which were identified in European and Asian ethnicities significantly confer risk for nsCL/P in Arab populations. Birth Defects Research (Part A) 100:307-313, 2014. (c) 2014 Wiley Periodicals, Inc.
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收藏
页码:307 / 313
页数:7
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