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Translational genomics of acquired laryngotracheal stenosis
Author(s) -
Anis Mursalin M.,
Zhao Zhigen,
Khurana Jasvir,
Krynetskiy Evgeny,
Soliman Ahmed M. S.
Publication year - 2014
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.24382
Subject(s) - single nucleotide polymorphism , genotyping , snp genotyping , snp , medicine , candidate gene , genotype , taqman , pathology , polymerase chain reaction , biology , genetics , gene
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