The functional SLC11A1 gene polymorphisms are associated with sarcoidosis in Turkish population

Abstract

Sarcoidosis (SA) is an immune-mediated multisystemic disorder of unknown etiology characterized by the accumulation of lymphocytes, mononuclear phagocytes and epithelioid cell granulomas involved in different organs and tissues. The belief that genetics contribute to SA etiology is supported by twin studies, disease clustering in families and racial differences in incidence rates. Involvements of SLC11A1 in macrophage function and activation, makes it an attractive candidate gene for immune-mediated and infectious diseases. We investigated the association between SA and four polymorphisms of the SLC11A1 gene, including a single nucleotide change in intron 4 (INT4); a nonconservative single-base substitution at codon 543 (D543N); a TGTG deletion in the 3' untranslated region; and the functional (GT)(n) repeat polymorphism in the 5' region, in 95 Turkish SA patients and 150 healthy controls, by using amplification refractory mutation system-polymerase chain reaction and sequencing. We found significant association between SA and INT4 G/C allele frequency (P = 0.0000; odds ratio 2.75; 95% confidence interval 1.68-4.52) and 5'(GT)(n) allele 2/3 frequency (P = 0.0000; odds ratio 2.69; 95% confidence interval 1.61-4.47) suggesting that SLC11A1 might be a plausible candidate gene for SA.

Genetics of Sarcoidosis

“…[69] This finding was replicated in Polish, Turkish and Greek cohorts where the opposite polymorphism (allele 3) was associated with increased risk of sarcoidosis. [70][71][72] In the Turkish cohort, polymorphism in INT4 was also associated with increased risk of sarcoidosis but this association was not noted in the other cohorts. [70] 3.…”

“…[70][71][72] In the Turkish cohort, polymorphism in INT4 was also associated with increased risk of sarcoidosis but this association was not noted in the other cohorts. [70] 3. Cytokines/Chemokines…”

c-Src kinase is involved in the tyrosine phosphorylation and activity of SLC11A1 in differentiating macrophages

“…Meta analysis identified the SLC11A1 locus as playing a role in influencing susceptibility to both infectious and autoimmune diseases [ 26 ]. The SLC11A1 gene has also been associated with rheumatoid arthritis [ 27 ], type 1 diabetes [ 28 ], sarcoidosis [ 29 ], Behçet’s syndrome [ 30 ], multiple sclerosis [ 31 ] and allergic asthma [ 32 ]. In addition, through its regulatory effect on the inflammatory cascade, it has been shown to play important roles in tissue regeneration and wound healing [ 32 , 33 ].…”

Μελέτη Πολυμορφισμών Ιντερλευκινών (IL) 12 Και 18 Και Του Γονιδίου BTNL2 Σε Έλληνες Πάσχοντες Από Σαρκοείδωση

“…Αντίθετα το αλλήλιο G ανιχνεύθηκε σε αυξημένη συχνότητα στην ομάδα των μαρτύρων 79% έναντι 68% στην ομάδα των ασθενών καθιστώντας αυτό το αλλήλιο πιθανό προστατευτικό παράγοντα στην εκδήλωση της σαρκοείδωσης. 88,123 Επίσης μελετήθηκε το γονίδιο SLC11A1(NRAMP1) το οποίο κωδικοποιεί την φυσική αντίσταση που σχετίζεται με την πρωτεΐνη 1 των μακροφάγων, και δεν επιβεβαιώθηκε η συσχέτισή του με την εκδήλωση της νόσου σε Αφροαμερικανούς, αλλά επιβεβαιώθηκε σε Πολωνούς ασθενείς 90 και Τούρκους 124 . Σε πρόσφατη μελέτη των Fischer A et al(2012) διαπιστώθηκε ένας νέος μονονουκλεοτιδικός πολυμορφισμός rs479777 στο χρωμόσωμα 11q13.1 που σχετίζεται με την σαρκοείδωση σε Ευρωπαίους, ενώ μέχρι πρόσφατα η παρουσία του συνδέονταν με την νόσο του Crohn, την ψωρίαση και την γυροειδή αλωπεκία.…”