Genetic Variation in Osteopontin Gene Is Associated with Susceptibility to Sarcoidosis in Slovenian Population

Abstract

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.

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

“…So far, genetic variants in the OPN gene have shown to be involved in susceptibility to other immune-mediated diseases such as SLE [59], [60], oligoarticular juvenile idiopathic arthritis [61] and sarcoidosis [51]. Despite promising functional data, previous genotype analyses could not confirm OPN as significant disease-modifying gene in classical Th17-mediated diseases such as multiple sclerosis [62], [63] and rheumatoid arthritis [64].…”

“…The selection of these SNPs was based on previous studies in which associations for several of these OPN variants with autoimmune and Th1- and Th17-mediated diseases have been shown [40], [41], [42], [43], [49], [50], [51], [52], [53]. The donor fluorescent molecule (fluorescein) at the 3′-end of the sensor probe (or the anchor probe in the case of rs2853744 and rs11730582) is excited at its specific fluorescence excitation wavelength (533 nm) and the energy is transferred to the acceptor fluorescent molecule at the 5′-end (LightCycler Red 610, 640 or 670) of the anchor probe (or the sensor probe in the case of rs2853744 and rs11730582).…”

A Study of the Association of Polymorphism rs5860110 and its Protective Role against Ankylosing Spondylitis in a Chinese Population

“…So far, genetic variants in the SPP1 gene have shown to be involved in susceptibility to other immune-mediated diseases such as SLE [8,9], oligoarticular juvenile idiopathic arthritis [26] and sarcoidosis [27]. Despite promising functional data, previous genotype analyses could not confirm SPP1 as significant disease modifying gene in classical Th17-mediated diseases such as multiple sclerosis [28,29] and rheumatoid arthritis [30].…”

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

“…In another study, Maver and colleagues [126] genotyped three OPN SNPs: rs11730582, rs11728697, and rs4754 in Slovenian patients and healthy subjects. The analysis revealed a signiicant diference in genotype frequencies at rs4754 SNP in patients and controls.…”