Variation in FGF1, FOXE1, and TIMP2genes is associated with nonsyndromic cleft lip with or without cleft palate

✍ Scribed by Tiit Nikopensius; Inga Kempa; Laima Ambrozaitytė; Triin Jagomägi; Mare Saag; Aušra Matulevičienė; Algirdas Utkus; Kaarel Krjutškov; Veronika Tammekivi; Linda Piekuse; Ilze Akota; Biruta Barkane; Astrida Krumina; Janis Klovins; Baiba Lace; Vaidutis Kučinskas; Andres Metspalu

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 112 KB
• Volume: 91
• Category: Article
• ISSN: 1542-0752
• DOI: 10.1002/bdra.20791

✦ Synopsis

Background:

Nonsyndromic cleft lip with or without cleft palate (cl/p) is a common complex birth defect caused by the interaction between multiple genes and environmental factors.

Methods:

Five hundred and eighty-seven single nucleotide polymorphisms in 40 candidate genes related to orofacial clefting were tested for association with cl/p in a clefting sample composed of 300 patients and 606 controls from estonian, latvian, and lithuanian populations.

Results:

In case-control comparisons, the minor alleles of fgf1 rs34010 (p = 4.56 × 10(-4) ), wnt9b rs4968282 (p = 0.0013), and foxe1 rs7860144 (p = 0.0021) were associated with a decreased risk of cl/p. multiple haplotypes in fgf1, foxe1, and timp2 and haplotypes in wnt9b, pvrl2, and lhx8 were associated with cl/p. the strongest association was found for protective haplotype rs250092/rs34010 gt in the fgf1 gene (p = 5.01 × 10(-4) ). the strongest epistatic interaction was observed between the col2a1 and wnt3 genes.

Conclusions:

Our results provide for the first time evidence implicating fgf1 in the occurrence of cl/p, and support timp2 and wnt9b as novel loci predisposing to cl/p. we have also replicated recently reported significant associations between variants in or near foxe1 and cl/p. it is likely that variation in foxe1, timp2, and the fgf and wnt signaling pathway genes confers susceptibility to nonsyndromic cl/p in northeastern european populations.