Rare variants in the TREX1 gene and susceptibility to autoimmune diseases.
TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE.
Department of Health Sciences, University of Eastern Piedmont, 28100 Novara, Italy ; Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, 28100 Novara, Italy.
Nadia
N
Barizzone
Sara
S
Monti
Simona
S
Mellone
Michela
M
Godi
Maurizio
M
Marchini
Raffaella
R
Scorza
Maria G
MG
Danieli
Sandra
S
D'Alfonso
D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000473:pathology
D010750:Phosphoproteins; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1