Affiliations: Institute of Medical Genetics, Department of
Obstetrics and Gynecology, University Medical Centre Ljubljana, 3,
Šlajmerjeva Street, Ljubljana 1000, Slovenia | Department of Pulmonary Diseases and Allergy,
University Medical Centre, 7, Zaloska Street, Ljubljana 1000, Slovenia
Note: [] Corresponding author: Professor Borut Peterlin, MD, PhD,
Institute of Medical Genetics, Department of Gynecology and Obstetrics,
University Medical Centre Ljubljana, Ljubljana Slovenia. Tel./Fax: +386 1
5401137; E-mail: [email protected]
Abstract: Sarcoidosis is a systemic inflammatory disease characterised by
appearance of granulomas. Precise etiology has not been elucidated. Osteopontin
(Opn) is a Th1 cytokine whose levels have been found increased in granulomas
and serum samples from patients with sarcoidosis. We investigated whether
genetic variation in Osteopontin gene (OPN) gene contributes to susceptibility
to sarcoidosis. Haplotype-block structure in the OPN gene region was investigated
using data from HapMap project. Three representative SNPs have been selected
from each block of SNPs in linkage disequilibrium (rs11730582-C/T,
rs11728697-C/T and rs4754-C/T). Genotyping was performed using TaqMan SNP
Genotyping Assays on a sample of 165 patients and 284 controls. Statistical
analyses of association were performed using Chi-Square test and algorithms
implemented in the haplo.stats and PHASE packages. Genotyping analysis revealed a significant difference in genotype
frequencies at rs4754 polymorphism in groups of patients and controls under
recessive genetic model (p=0.036, OR=1.99, 95%CI=1.04–3.82), CC
homozygotes being significantly over-represented in the patients group. However
these results failed to reach significance after correction for multiple
testing (p=0.25). The frequencies of predicted haplotypes differed between
patient and control groups, frequency of TTT haplotype was found to be
significantly decreased in the group of patients with sarcoidosis (p=0.014,
OR=0.40, 95%CI=0.20–0.79). Our results suggest that variation in the OPN gene might be
significantly associated with sarcoidosis and that the TTT haplotype in OPN may
act as a protective factor in sarcoidosis.
Keywords: Sarcoidosis, osteopontin, polymorphism, haplotype, association study
