Association between CD14 gene polymorphisms and disease phenotype in sarcoidosis
Zvi G Fridlender1, Asaf Schwartz, Martin Kohan
1Institute of Pulmonology, Hadassah-Hebrew University, Jerusalem 91120, Israel. fridlender@hadassah.org.il
Respiratory Medicine
|May 1, 2010
Summary
Genetic variations in CD14 (a lipopolysaccharide receptor component) are linked to sarcoidosis. Higher soluble CD14 levels and specific genotypes correlate with disease presentation and severity.
Area of Science:
- Immunology
- Genetics
- Pulmonology
Background:
- Sarcoidosis etiology is unknown, but genetic factors are implicated.
- Granuloma formation in sarcoidosis suggests shared pathways with Crohn's Disease.
- Previous studies suggest a link between sarcoidosis and CD14, a component of the lipopolysaccharide receptor.
Purpose of the Study:
- To investigate the association between the CD14 gene promoter 159 C-->T polymorphism and soluble CD14 levels in sarcoidosis patients.
- To explore correlations between sarcoidosis clinical phenotypes, genotypes, and soluble CD14 levels.
Main Methods:
- Genotyping of the CD14 gene promoter 159 C-->T polymorphic site in 74 sarcoidosis patients and 85 healthy controls.
- Measurement of serum soluble CD14 levels in the study cohort.
- Analysis of correlations between genotype, soluble CD14 levels, and clinical parameters (age of onset, disease severity, pulmonary function).
Main Results:
- The TT genotype of the CD14 gene promoter was significantly more prevalent in sarcoidosis patients (p=0.03).
- Serum soluble CD14 levels were elevated in sarcoidosis patients compared to controls (p=0.001).
- Within the sarcoidosis cohort, CC homozygous patients exhibited older age at presentation, milder disease (lower SAC score), longer time to diagnosis, and less pulmonary function impairment.
Conclusions:
- The study suggests a role for CD14 in sarcoidosis pathogenesis.
- A significant association between CD14 genotype and clinical phenotype in sarcoidosis was identified.
- Further research is warranted to elucidate the precise role of CD14 in sarcoidosis etiology, pathogenesis, and clinical manifestations.
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