Chitotriosidase deficiency in the Cypriot population: Identification of a novel deletion in the CHIT1 gene.

Objectives: The purpose of this study was to determine the normal range of chitotriosidase activity in the Cypriot population and the frequency of the 24bp duplication polymorphism. Furthermore, we compared the allele frequency of this polymorphism in two locations with different malaria endemicity in the past.

Design And Methods: Plasma chitotriosidase activity was measured using a fluorogenic substrate. The 24bp polymorphism was detected using PCR analysis of exon 10 of the CHIT1 gene. Additional mutations were detected using direct sequencing.

Results: The normal range of chitotriosidase activity was found to be 9.5-44.0nmol/ml/hr. Among 114 normal individuals genotyped for the 24bp duplication, 7% were found to be homozygous, 36% heterozygous and 57% wild type (allele frequency 0.25). The allele frequency of this polymorphism in individuals originating from two locations with different malaria endemicity in the past was not significantly different. A novel deletion mutation in the CHIT1 gene was identified associated with loss of chitotriosidase activity. This new deletion eliminates 29 nucleotides from exon 9 resulting in the generation of a premature stop codon, probably leading to the production of an aberrant protein molecule.

Conclusions: The normal range of chitotriosidase activity and the allele frequency of the 24bp duplication polymorphism in the Cypriot population were found to be similar to those of other Mediterranean populations. No evidence for an association between the presence of the 24bp duplication polymorphism and susceptibility to malaria was found. A novel deletion in exon 9 of the CHIT1 gene was identified (allele frequency 0.01).