BACKGROUND: Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined. OBJECTIVE: To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor alpha (IL4RA), IL-13, and CD14 promoter genes are associated with DA. METHODS: Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes. RESULTS: No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the IL4RA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01). CONCLUSIONS: Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.
BACKGROUND:Diisocyanateasthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined. OBJECTIVE: To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor alpha (IL4RA), IL-13, and CD14 promoter genes are associated with DA. METHODS: Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes. RESULTS: No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the IL4RA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01). CONCLUSIONS: Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.
Authors: Jean-Luc Malo; Susan M Tarlo; Joaquin Sastre; James Martin; Mohamed F Jeebhay; Nicole Le Moual; Dick Heederik; Thomas Platts-Mills; Paul D Blanc; Olivier Vandenplas; Gianna Moscato; Frédéric de Blay; André Cartier Journal: Ann Am Thorac Soc Date: 2015-07
Authors: David I Bernstein; Grace E Kissling; Gurjit Khurana Hershey; Berran Yucesoy; Victor J Johnson; André Cartier; Denyse Gautrin; Joaquin Sastre; Louis-Philippe Boulet; Jean-Luc Malo; Santiago Quirce; Susan M Tarlo; Stacy Langmeyer; Michael I Luster; Zana L Lummus Journal: J Allergy Clin Immunol Date: 2011-04-13 Impact factor: 10.793
Authors: David I Bernstein; Michael Kashon; Zana L Lummus; Victor J Johnson; Kara Fluharty; Denyse Gautrin; Jean-Luc Malo; André Cartier; Louis-Philippe Boulet; Joaquin Sastre; Santiago Quirce; Dori Germolec; Susan M Tarlo; Maria-Jesus Cruz; Xavier Munoz; Michael I Luster; Berran Yucesoy Journal: Toxicol Sci Date: 2012-09-13 Impact factor: 4.849
Authors: Berran Yucesoy; Kenneth M Kaufman; Zana L Lummus; Matthew T Weirauch; Ge Zhang; André Cartier; Louis-Philippe Boulet; Joaquin Sastre; Santiago Quirce; Susan M Tarlo; Maria-Jesus Cruz; Xavier Munoz; John B Harley; David I Bernstein Journal: Toxicol Sci Date: 2015-04-26 Impact factor: 4.849