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Duplication in CHIT1 gene and the risk for aspergillus lung disease in CF patients

Authors

  • Galit Livnat MD,

    1. Pediatric Pulmonary Unit, Meyer Children's Hospital, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
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  • Ronen Bar-Yoseph MD,

    1. Pediatric Pulmonary Unit, Meyer Children's Hospital, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
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  • Adi Mory PhD,

    1. Genetic Institute, Meyer Children's Hospital, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
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  • Efrat Dagan PhD,

    1. Genetic Institute, Meyer Children's Hospital, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
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  • Nael Elias MD,

    1. Pediatric Pulmonary Unit, Meyer Children's Hospital, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
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  • Ruth Gershoni MD,

    1. Genetic Institute, Meyer Children's Hospital, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
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  • Prof. Lea Bentur MD

    Corresponding author
    1. Pediatric Pulmonary Unit, Meyer Children's Hospital, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
    • Correspondence to: Director, Pediatric Pulmonology Unit, Clinical Associate Professor of Pediatrics and Pediatric Pulmonology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel. E-mail: l_bentur@rambam.health.gov.il

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  • Conflict of interest: None.
  • Clinical Trial Registration: The study was approved by the Rambam Health Care Campus IRB committee (No. 450-10) and registered at http://clinicaltrials.gov: identifier NCT01572870. Informed consent was obtained for each patient.

Abstract

Background

Aspergillus often persists in the respiratory tract of patients with Cystic Fibrosis (CF) and may cause allergic broncho-pulmonary aspergillosis (ABPA). Chitinases are enzymes that digest the chitin polymer. Plants use chitinase as a defense mechanism against fungi. Chitotriosidase (CHIT1) is the major chitinase in human airways. Variation in the coding region with 24-bp duplication allele results in reduced CHIT1 activity. Recently, CHIT1 duplication heterozygocity was found in 6/6 patients with severe asthma and fungal sensitization (SAFS).

Aim

Our aim was to evaluate the link between CHIT1 duplication in CF patients and the predisposition to Allergic broncho-pulmonary mycosis (ABPM) or persistent Aspergillus positive sputum (APS).

Patients and Methods

CHIT1 duplication was assessed in three CF groups. Group 1: patients who had neither ABPM nor APS in the past (control group). Group 2: patients with persistent APS (≥2/year), without ABPA. Group 3: patients with current or past ABPM.

Results

Forty patients with CF were included in the analysis, CHIT1 duplication heterozygocity was found in 3/6 (50%) of the patients in the ABPM group, 3/12 (25%) in the APS group, and 7/22 (31.8%) in the control group (P > 0.05). Eleven patients carried W1282X mutation, 90.9% were negative for CHIT1 duplication, five of them were homozygous for W1282X; none of them had CHIT1 duplication or ABPM.

Conclusions

CHIT1 duplication is not found in all CF patients with ABPM in contrast to patients with SAFS. These results suggest that CHIT1 duplication cannot be the sole explanation for Aspergillus positive sputum in CF patients. Pediatr Pulmonol. 2014; 49:21–27. © 2013 Wiley Periodicals, Inc.

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