Association between SLC11A1 (formerly NRAMP1) and the risk of sarcoidosis in Poland

Abstract

Sarcoidosis (SA) is a systemic granulomatous disorder of unknown etiology characterized by T helper 1-type inflammatory responses at sites of disease with signs of B cell hyperactivity. Like rheumatoid arthritis and diabetes, an infectious etiology has frequently been postulated but no single infectious trigger definitively identified. Polymorphic alleles at SLC11A1 have previously been associated with susceptibility to both the putative infectious agents and to these autoimmune disorders. We therefore investigated its candidacy as a genetic determinant of SA in Poland in an association-based study comparing 86 SA patients with 85 tuberculosis (TB) patients and 93 control subjects. The functional promoter (GT) n polymorphism and four of 10 other single nucleotide or insertion/deletion polymorphisms genotyped across SLC11A1 were informative in our sample. Consistent with previous autoimmune disease studies, allele 3 at the functional (GT) n promoter region repeat polymorphism was significantly associated with SA when compared with healthy controls (odds ratio 1.68; 95% CI: 1.01-2.81; P ¼ 0.04) or with TB patients (odds ratio 1.69; 95% CI: 1.042-0.78; P ¼ 0.03).

Mycobacterium tuberculosis Complex and Mycobacterial Heat Shock Proteins in Lymph Node Tissue from Patients with Pulmonary Sarcoidosis

“…A possible explanation for this is that the assay for IS6110 may not have been sufficiently sensitive to detect the very small quantity of M. tuberculosis genome in tissue from SA patients or that M. tuberculosis is present but the strains do not contain IS6110. Another possible explanation for the negative molecular results is that a small numbers of organisms provoke an intense inflammatory response, analogous to tuberculoid leprosy (3,4). It is also suggested that the agents associated with sarcoidosis are not whole mycobacteria but their antigens, e.g., mycobacterial hsp (7,8).…”

A CXCL2 tandem repeat promoter polymorphism is associated with susceptibility to severe sepsis in the Spanish population

“…However, some experiments demonstrated that the STRs located in the proximity or within a gene can regulate gene expression 40 that may cause human diseases. 41 Recently, different studies [42][43][44] have reported that common alleles of dinucleotide STRs, whose length variation are known to modulate promoter activity, conferred susceptibility to diseases. In the same way, D4S3454 within the CXCL2 promoter could be playing an important role in the regulation of transcription.…”

Environmental Triggers of Type 1 Diabetes Mellitus – Mycobacterium Avium Subspecies Paratuberculosis

“…Sarcoidosis, the previously mentioned systemic disease associated with MAP, is also associated with polymorphisms of the SLC11A1 gene (Dubaniewicz et al, 2005). Susceptibility to mycobacterial diseases tuberculosis, leprosy and Buruli's ulcer are associated with polymorphism of the SLC11A1 gene (Stienstra et al, 2006).…”