Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Three prime Repair Exonuclease 1 (TREX-1) is an exonuclease involved in DNA repair preventing genomic instability. TREX-1 variants have been previously associated with activation of type I interferon (IFN) pathway in patients with Aicardi-Goutieres syndrome, as well as in Familial chilblain lupus. Primary Sjogren’s syndrome (SS) -a chronic autoimmune disorder affecting the exocrine glands with a high predilection for B-cell lymphoma development- is also characterized by the presence of type I IFN signature in approximately half of affected individuals. The goal of the present study was to explore whether TREX-1 variants rs11797 (A>G, p.Y177Y), 5’UTR rs3135941 (C>T, NG_009820.1:g.5439T>C) and rs3135945 (intronic, G>A) polymorphisms could influence the risk of SS and SS related lymphoma.
Three single nucleotide polymorphisms (SNPs) of the TREX-1 gene (rs11797, rs3135941 and the rs3135945) were evaluated in 229 SS-non lymphoma, 89 SS-lymphoma (19 non-MALT, 70 SS-MALT) and 240 healthy controls (HC) by PCR-based assays. All patients were followed in the Department of Pathophysiology, School of Medicine and the Department of Rheumatology, General Hospital of Athens between 2008-2014 and fulfilled the 2002 American/European criteria for the classification of primary SS. Allele and genotype frequencies in primary SS patients and HC were determined by SHEsis and SNPStats software.
No statistically significant differences were detected in the frequency of the above SNPs tested between SS-non lymphoma, SS-lymphoma patients and HC (p>0.05). However, SS non-MALT lymphoma patients had significantly increased prevalence of the SNP rs11797 G allele compared to HC (OR: 2.28, p=0.02). Of interest, the presence of the GC haplotype (rs11797 and rs3135941) conferred increased susceptibility for SS-non MALT lymphoma patients compared to both HC and SS-non lymphoma patients [OR 95% (CI): 2.33 (1.01-5.36), p=0.04 and 1.53 (1.02-2.28), p=0.04, respectively). The TREX-1 SNP rs3135945 was observed in 1/257 SS patients but not in the HC group.
Increased frequency of the TREX-1 GC haplotype (rs11797 and rs3135941) in SS individuals complicated by non-MALT lymphoma may imply impaired DNA repair as an additional mechanism for SS-related lymphomagenesis.
To cite this abstract in AMA style:Makri P, Nezos A, Voulgarelis M, Moutsopoulos HM, Mavragani C. TREX-1 Variants in Sjögren’s Syndrome Related Lymphomagenesis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/trex-1-variants-in-sjogrens-syndrome-related-lymphomagenesis/. Accessed February 26, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/trex-1-variants-in-sjogrens-syndrome-related-lymphomagenesis/