Duplication in CHIT1 gene and the risk for Aspergillus lung disease in CF patients.
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).


OBJECTIVE
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).


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.
Pediatric Pulmonary Unit, Meyer Children's Hospital, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Galit
G
Livnat
Ronen
R
Bar-Yoseph
Adi
A
Mory
Efrat
E
Dagan
Nael
N
Elias
Ruth
R
Gershoni
Lea
L
Bentur
D000293:Adolescent; D001230:Aspergillus / Q000302:isolation & purification; D001249:Asthma / Q000235:genetics; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D006579:Heterozygote; D006596:Hexosaminidases / Q000235:genetics*; D006801:Humans; D008297:Male; D055732:Pulmonary Aspergillosis / Q000150:complications*; D013183:Sputum / Q000382:microbiology; D055815:Young Adult
D006596:Hexosaminidases; C086400:chitotriosidase
Aspergillus; CF; CHIT1