TREX-1 Variants in Sjögren's Syndrome Related Lymphomagenesis

Panagiota Makri¹, Adrianos Nezos², Michael Voulgarelis³, Haralampos M. Moutsopoulos⁴ and Clio Mavragani⁵, ¹Physiology, Department of Physiology, School of Medicine, University of Athens, Athens, Greece, ²Physiology, Department of Experimental Physiology, School of Medicine, National Kapodistrian University of Athens, Athens, Greece, ³Pathophysiology, Department of Pathophysiology, Medical School of Athens, Athens, Greece, ⁴Department of Pathophysiology, Medical School of Athens, Department of Pathophysiology, Athens, Greece, ⁵Physiology, Department of Physiology, School of Medicine, National Kapodistrian University of Athens, Athens, Greece

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: MALT lymphoma, Sjogren's syndrome and genetics

Session Information

Date: Tuesday, November 10, 2015

Title: Sjögren's Syndrome: Translational Insights into Sjögren's Syndrome

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

Disclosure: P. Makri, None; A. Nezos, None; M. Voulgarelis, None; H. M. Moutsopoulos, None; C. Mavragani, None.

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 .

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