CHIT1 genetic defects in the Portuguese population

Area of Science:

• Biochemistry
• Genetics
• Human Physiology

Background:

• Chitotriosidase is a macrophage-secreted enzyme used as a biomarker for lysosomal and nonlysosomal diseases.
• Genetic mutations in the chitotriosidase gene (CHIT1) can impact the reliability of this biomarker.
• Limited data exists on the molecular spectrum of CHIT1 genetic variations, especially within specific populations.

Purpose of the Study:

• To investigate the genetic variation of the CHIT1 gene in a specific population group.
• To identify and characterize CHIT1 mutations and polymorphisms.
• To determine the frequency of specific CHIT1 variants, particularly in the Portuguese population.

Main Methods:

• Analysis of CHIT1 mutations in ten normal controls.
• Identification of missense alterations using genetic sequencing.
• Allelic discrimination assays to test a larger cohort of 503 individuals from the Portuguese population.

Main Results:

• Six missense alterations in the CHIT1 gene were detected in normal controls.
• The G102S polymorphism, known for altered catalytic properties, was the most frequent variant in controls (4/10).
• In the Portuguese population sample (n=503), the G102S variant was present in 49.5% of individuals with an allele frequency of 0.29.

Conclusions:

• The CHIT1 gene exhibits considerable genetic variability.
• The G102S polymorphism is highly frequent in the Portuguese population.
• Understanding CHIT1 genetic variations is crucial for accurate interpretation of chitotriosidase as a biomarker.