title: Epidermal growth factor receptor (EGFR) pathway genes and interstitial lung disease: an association study.
abstract: The etiology and pathogenesis of idiopathic interstitial lung disease (ILD) remain incompletely understood. Genetic susceptibility to ILD has been demonstrated in previous studies. It is well known that EGFR inhibitors can induce ILD in human lung cancer patient with ethnic differences, which prompted us to hypothesize that genetic variation in EGFR pathway genes confer susceptibility to ILD. We aimed in this study to investigate whether functional polymorphisms of EGFR and its ligands genes (EGF and TGFA) were associated with ILD. Three EGFR [-216G/T (rs712830), -191A/C (rs712829), 497R > K(A/G) (rs2227983)], one EGF [61A/G, (rs4444903)] and one TGFA (rs3821262C/T) polymorphisms previously demonstrated to alter gene functions were genotyped in 229 sporadic idiopathic ILD patients and 693 normal healthy individuals. Allelic and genotypic association tests between these polymorphisms and ILD were performed. The EGF 61A/G polymorphism was significantly associated with elevated risk of ILD, with the frequency of G allele significantly increased in the ILD patient population (OR = 1.33, 95%CI = 1.07-1.66, P = 0.0099). None of the other polymorphisms were associated with risk of ILD. Our study suggested that the EGF 61A/G polymorphism may be associated with sporadic ILD. While a false positive finding cannot be excluded, independent studies are warranted to further validate this result.
authors.affiliation: 1] Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy,Purdue University, West Lafayette, Indiana [2] Department of Respiratory Medicine, the Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy,Purdue University, West Lafayette, Indiana.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wei
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine; Purdue University, West Lafayette, Indiana.
authors.forename: Yava L
authors.initials: YL
authors.lastname: Jones-Hall
authors.affiliation: Center for Immunobiology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Ragini
authors.initials: R
authors.lastname: Vittal
authors.affiliation: Department of Statistics, Purdue University, West Lafayette, Indiana.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 1] Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy,Purdue University, West Lafayette, Indiana [2] Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Liu
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004815:Epidermal Growth Factor / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012306:Risk; D012307:Risk Factors
chemical_list: D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors