Translational genomics of acquired laryngotracheal stenosis

Authors

  • Mursalin M. Anis MD, PhD,

    1. Department of Otolaryngology–Head and Neck Surgery, and the Temple University School of Pharmacy, Philadelphia, Pennsylvania, U.S.A
    Search for more papers by this author
  • Zhigen Zhao PhD,

    1. Department of Statistics, Fox School of Business, Temple University, Philadelphia, Pennsylvania, U.S.A
    Search for more papers by this author
  • Jasvir Khurana MD,

    1. Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania, U.S.A
    Search for more papers by this author
  • Evgeny Krynetskiy PhD, DSc,

    1. the Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania, U.S.A.
    Search for more papers by this author
  • Ahmed M. S. Soliman MD

    Corresponding author
    1. Department of Otolaryngology–Head and Neck Surgery, and the Temple University School of Pharmacy, Philadelphia, Pennsylvania, U.S.A
    • Send correspondence to Ahmed M. S. Soliman, MD, Department of Otolaryngology–Head and Neck Surgery, Temple University School of Medicine, 3440 N. Broad Street, Kresge West 312, Philadelphia, PA 19140. E-mail: asoliman@temple.edu

    Search for more papers by this author

  • Presented as a poster at the American Laryngological Association's 2013 Spring Meeting Orlando, Florida, U.S.A., April 10–11, 2013.

  • The authors have no funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis

Acquired laryngotracheal stenosis (ALTS) results from abnormal mucosal wound healing after laryngeal and/or tracheal injury. Patients with ALTS often present late after significant reduction of the airway lumen and onset of symptoms. Motivated by the need for earlier detection of affected patients, we sought to investigate genetic markers for ALTS that would identify susceptible patients.

Study Design

Pilot Case-Control Study.

Methods

Seventy-six patients were recruited, 40 patients with ALTS and 36 control patients with airway injury but without ALTS. DNA was isolated from whole blood and formalin-fixed paraffin-embedded specimens from patients. Custom primers were designed and the TaqMan assay employing allele-specific polymerase chain reaction was used to interrogate single nucleotide polymorphisms (SNPs): rs2569190, rs1799750, and rs1800469 located in candidate genes CD14, matrix metalloproteinase-1 (MMP-1), and transforming growth factor-β1 (TGF-β1), respectively. A logistic regression model was used to examine the association of candidate gene polymorphisms with the presence or absence of ALTS.

Results

All 76 patients were successfully genotyped at the three loci of interest by optimizing the genotyping protocol. MMP-1 SNP rs1799750 was most significantly associated with development of ALTS (P = 0.005).

Conclusion

Identification of SNPs associated with development of ALTS will provide new experimental targets to study wound healing in human subjects. The association found in the current study between ALTS and SNP rs1799750 is being validated in a larger population examining an expanded set of relevant SNPs. Identifying patients with genetic susceptibility to ALTS and poor wound healing in the upper airway will be useful for management of patients after upper-airway injury.

Level of Evidence

N/A. Laryngoscope, 124:E175–E179, 2014

Ancillary