Translational genomics of acquired laryngotracheal stenosis. (20th February 2014)

• Record Type: Journal Article
• Authors: Anis, Mursalin M.; Zhao, Zhigen; Khurana, Jasvir; Krynetskiy, Evgeny; Soliman, Ahmed M. S.
• Is Part Of: Laryngoscope. Volume 124:Number 5(2014:May)
• Page Start: E175
• Page End: E179
• Publication Date: 2014-02-20
• Subjects: Otolaryngology -- Periodicals; 617.51005
• DOI: 10.1002/lary.24382
• Languages: English
• ISSNs: 0023-852X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="lary24382-sec-0001" sec-type="section"> <title>Objectives/Hypothesis</title> <p>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.</p> </sec> <sec id="lary24382-sec-0002" sec-type="section"> <title>Study Design</title> <p>Pilot Case‐Control Study.</p> </sec> <sec id="lary24382-sec-0003" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="lary24382-sec-0004" sec-type="section"> <title>Results</title> <p>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 (<italic>P</italic> = 0.005).</p> </sec> <sec id="lary24382-sec-0005" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> <sec id="lary24382-sec-0006" sec-type="section"> <title>Level of Evidence</title> <p>N/A. <italic>Laryngoscope</italic>, 124:E175–E179, 2014</p> </sec> </abstract>