Translational genomics of acquired laryngotracheal stenosis.
OBJECTIVE
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.


METHODS
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).


CONCLUSIONS
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.
Department of Otolaryngology-Head and Neck Surgery, and the Temple University School of Pharmacy, Philadelphia, Pennsylvania, U.S.A.
Mursalin M
MM
Anis
Zhigen
Z
Zhao
Jasvir
J
Khurana
Evgeny
E
Krynetskiy
Ahmed M S
AM
Soliman
D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D023281:Genomics; D005838:Genotype; D006801:Humans; D007442:Intubation, Intratracheal / Q000009:adverse effects; D007829:Laryngostenosis / Q000235:genetics*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D014135:Tracheal Stenosis / Q000235:genetics*
C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
Laryngotracheal stenosis encompasses: laryngeal stenosis; genetics; subglottic stenosis; tracheal stenosis; wound healing