MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate

  1. Triin Jagomägi1,†,
  2. Tiit Nikopensius2,3,†,
  3. Kaarel Krjutškov2,3,
  4. Veronika Tammekivi3,
  5. Triin Viltrop2,
  6. Mare Saag1,
  7. Andres Metspalu2,3,4

Article first published online: 11 MAY 2010

DOI: 10.1111/j.1600-0722.2010.00729.x

Issue

European Journal of Oral Sciences

European Journal of Oral Sciences

Volume 118, Issue 3, pages 213–220, June 2010

Additional Information

How to Cite

Jagomägi, T., Nikopensius, T., Krjutškov, K., Tammekivi, V., Viltrop, T., Saag, M. and Metspalu, A. (2010), MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate. European Journal of Oral Sciences, 118: 213–220. doi: 10.1111/j.1600-0722.2010.00729.x

Author Information

  1. 1

    Department of Stomatology, Faculty of Medicine, University of Tartu, Tartu, Estonia

  2. 2

    Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

  3. 3

    Estonian Biocentre, Tartu, Estonia

  4. 4

    Estonian Genome Center, University of Tartu, Tartu, Estonia

  1. †

    Authors who contributed equally to the work presented in this manuscript.

*Triin Jagomägi, Department of Stomatology, Faculty of Medicine, University of Tartu, Kastani 16, Tartu 50410, Estonia Telefax: +37–27–319856 E-mail: triin.jagomagi@ortodontia.ee

Publication History

  1. Issue published online: 11 MAY 2010
  2. Article first published online: 11 MAY 2010
  3. Accepted for publication February 2010

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Keywords:

  • Arrayed Primer Extension method (APEX);
  • case–control association study;
  • genotyping;
  • nonsyndromic cleft lip with or without cleft palate;
  • single nucleotide polymorphism (SNP)

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 Sci

Recent 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.

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