Single nucleotide polymorphism associated with nonsyndromic cleft palate influences the processing of miR-140

Authors

  • Ling Li,

    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
    Search for more papers by this author
  • Tian Meng,

    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
    Search for more papers by this author
  • Zhonglin Jia,

    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
    Search for more papers by this author
  • Guiquan Zhu,

    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
    Search for more papers by this author
  • Bing Shi

    Corresponding author
    1. State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China
    2. Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China
    • Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, No. 14, Section 3, RenMinNan Road, Chengdu 610041, PR China.
    Search for more papers by this author

  • How to cite this article: Li L, Meng T, Jia Z, Zhu G, Shi B. 2010. Single nucleotide polymorphism associated with nonsyndromic cleft palate influences the processing of miR-140. Am J Med Genet Part A 152A:856–862.

Abstract

Nonsyndromic oral cleft is a common developmental malformation of humans. Embryonic development is regulated by microRNAs. MicroRNA-140-5p (miR-140-5p) was found to regulate palatal development. As sequence variants in miRNA genes are likely to affect miRNA expression and/or maturation, we investigated the miRNA-140 gene and identified a SNP (rs7205289: C>A) located in precursor miRNA-140. We carried out a case–control analysis in 557 patients with nonsyndromic oral clefts and 306 unaffected controls from west China and found that the frequency of minor allele (A allele) was significantly increased (P = 0.003 after Bonferroni correction) in nonsyndromic cleft palate (NSCP) patients in comparison with that in controls. We constructed expression vectors of primary miRNA-140 (pri-miR-140) with the major and minor alleles of rs7205289. The vectors were transfected into HEK293 cells, and the mature forms of miR-140 were detected by Northern blot. Compared to the vector with the C allele, the vector with the A allele was found to influence the miR-140 processing, resulting in a significant decrease of miR-140-5p and an increase of miR-140-3p. These results suggest that the SNP located in pre-miR-140 contributes to NSCP susceptibility by influencing the processing of miR-140. © 2010 Wiley-Liss, Inc.

Ancillary