Triin Jagomägi1,2, Tiit Nikopensius1,3,4, Kaarel Krjutškov3,4, Veronika Tammekivi3, Triin Viltrop4, Mare Saag2, Andres Metspalu3,5,4
1Authors who contributed equally to the work presented in this manuscript.
2Department of Stomatology, Faculty of Medicine, University of Tartu, Tartu, Estonia
3Estonian Biocentre, Tartu, Estonia
4Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
5Estonian Genome Center, University of Tartu, Tartu, Estonia
Tóm tắt
Jagomägi T, Nikopensius T, Krjutškov K, Tammekivi V, Viltrop T, Saag M, Metspalu A. MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate. Eur J Oral Sci 2010; 118: 213–220. © 2010 The Authors. Journal compilation©2010 Eur J Oral SciRecent studies suggest that multiple interacting loci, with possible additional environmental factors, influence the risk for nonsyndromic oral clefts, one of the most common birth defects in humans. Advances in high‐throughput genotyping technology allow the testing of multiple markers, simultaneously, in many candidate genes. We tested for associations between 176 haplotype‐tagging single nucleotide polymorphisms (SNPs) in 18 candidate genes/loci and nonsyndromic clefts in a case–control study in an Estonian sample (153 patients, 205 controls). The most significant associations with nonsyndromic cleft lip with or without cleft palate (CL/P) were found for SNPs in MSX1, MTHFR, and PVRL2, including several common haplotypes in the MTHFR and MSX1 genes. The strongest association was observed for rs6446693 in the MSX1 region, which remained statistically significant after Bonferroni correction. The strongest association with nonsyndromic cleft palate (CP) was found for the SNP rs11624283 in the JAG2 gene. Epistatic interactions were observed for SNPs within PVRL2, between BCL3 and EDN1, and between IRF6 and MSX1 genes. This study provides further evidence implicating MSX1 and MTHFR in the etiology of nonsyndromic CL/P across different populations.
