Association of ultraviolet radiation resistance‑associated gene polymorphisms with rheumatoid arthritis

Kim,Hyung‑Ki; Lee,Wha‑Young; Kwon,Jun‑Tack; Sohn,Dong‑Ryul; Hong,Seung‑Jae; Kim,Hak‑Jae

doi:10.3892/br.2013.185

Association of ultraviolet radiation resistance‑associated gene polymorphisms with rheumatoid arthritis

Authors:
- Hyung‑Ki Kim
- Wha‑Young Lee
- Jun‑Tack Kwon
- Dong‑Ryul Sohn
- Seung‑Jae Hong
- Hak‑Jae Kim
View Affiliations

Affiliations: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea, Soonchunhyang Medical Research Institute, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea, Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
Published online on: October 21, 2013 https://doi.org/10.3892/br.2013.185
Pages: 117-121

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The ultraviolet radiation resistance‑associated gene (UVRAG) protein binds to the Beclin 1̸PI3‑kinase III complex and promotes autophagy. Autophagy may be upregulated by endoplasmic reticulum (ER) stress. Persistent and excessive ER stress may alter synovial fibroblast apoptosis and this alteration may affect the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated whether UVRAG genetic polymorphisms are associated with RA. To determine the association between UVRAG polymorphisms and RA, we genotyped five UVRAG single‑nucleotide polymorphisms (SNPs; rs7111334, intron C̸T; rs7933235, intron A̸G; rs1380075, intron T̸A; rs1458836, near the 5' gene terminal G̸A; and rs636420, exon 15 C̸T) using a direct sequencing method in 243 RA patients and 417 control subjects. Among these, one SNP (rs7111334) exhibited significant genotypic̸allelic differences between RA patients and the control group. Therefore, this study suggested a possible association between UVRAG polymorphisms and RA susceptibility.

View Figures

View References

1	Teitz T, Penner M, Eli D, et al: Isolation by polymerase chain reaction of a cDNA whose product partially complements the ultraviolet sensitivity of xeroderma pigmentosum group C cells. Gene. 87:295–298. 1990. View Article : Google Scholar
2	Liang C, Feng P, Ku B, Dotan I, Canaani D, Oh BH and Jung JU: Autophagic and tumour suppressor activity of a novel Beclin 1-binding protein UVRAG. Nat Cell Biol. 8:688–699. 2006. View Article : Google Scholar : PubMed/NCBI
3	Liang C, Lee JS, Inn KS, et al: Beclin 1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol. 10:776–787. 2008. View Article : Google Scholar : PubMed/NCBI
4	Yin X, Cao L, Peng Y, et al: A critical role for UVRAG in apoptosis. Autophagy. 7:1242–1244. 2011. View Article : Google Scholar : PubMed/NCBI
5	Munz C: Enhancing immunity through autophagy. Annu Rev Immunol. 27:423–449. 2009. View Article : Google Scholar : PubMed/NCBI
6	Deretic V: Autophagy in innate and adaptive immunity. Trends Immunol. 26:523–528. 2005. View Article : Google Scholar : PubMed/NCBI
7	Levine B and Deretic V: Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol. 7:767–777. 2007. View Article : Google Scholar : PubMed/NCBI
8	Levine B, Mizushima N and Virgin HW: Autophagy in immunity and inflammation. Nature. 469:323–335. 2011. View Article : Google Scholar : PubMed/NCBI
9	Virgin HW and Levine B: Autophagy genes in immunity. Nat Immunol. 10:461–470. 2009. View Article : Google Scholar : PubMed/NCBI
10	Zhou XJ and Zhang H: Autophagy in immunity: implications in etiology of autoimmune/autoinflammatory diseases. Autophagy. 8:1286–1299. 2012. View Article : Google Scholar : PubMed/NCBI
11	Kouroku Y, Fujita E, Tanida I, et al: ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ. 14:230–239. 2007. View Article : Google Scholar : PubMed/NCBI
12	Tobon GJ, Youinou P and Saraux A: The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis. Autoimmun Rev. 9:A288–A292. 2010. View Article : Google Scholar : PubMed/NCBI
13	Korb A, Pavenstadt H and Pap T: Cell death in rheumatoid arthritis. Apoptosis. 14:447–454. 2009. View Article : Google Scholar : PubMed/NCBI
14	Nakamachi Y, Kawano S, Takenokuchi M, et al: MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum. 60:1294–1304. 2009. View Article : Google Scholar : PubMed/NCBI
15	Shin YJ, Han SH, Kim DS, et al: Autophagy induction and CHOP under-expression promotes survival of fibroblasts from rheumatoid arthritis patients under endoplasmic reticulum stress. Arthritis Res Ther. 12:R192010. View Article : Google Scholar
16	Liu H, Bowes RC III, van de Water B, Sillence C, Nagelkerke JF and Stevens JL: Endoplasmic reticulum chaperones GRP78 and calreticulin prevent oxidative stress, Ca²⁺disturbances, and cell death in renal epithelial cells. J Biol Chem. 272:21751–21759. 1997. View Article : Google Scholar : PubMed/NCBI
17	Egger L, Schneider J, Rheme C, Tapernoux M, Hacki J and Borner C: Serine proteases mediate apoptosis-like cell death and phagocytosis under caspase-inhibiting conditions. Cell Death Differ. 10:1188–1203. 2003. View Article : Google Scholar : PubMed/NCBI
18	Kim I, Xu W and Reed JC: Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 7:1013–1030. 2008. View Article : Google Scholar : PubMed/NCBI
19	McCullough KD, Martindale JL, Klotz LO, Aw TY and Holbrook NJ: Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol. 21:1249–1259. 2001. View Article : Google Scholar : PubMed/NCBI
20	Rao RV, Ellerby HM and Bredesen DE: Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 11:372–380. 2004. View Article : Google Scholar : PubMed/NCBI
21	Arnett FC, Edworthy SM, Bloch DA, et al: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 31:315–324. 1988. View Article : Google Scholar : PubMed/NCBI
22	Jeong TJ, Shin MK, Uhm YK, Kim HJ, Chung JH and Lee MH: Association of UVRAG polymorphisms with susceptibility to non-segmental vitiligo in a Korean sample. Exp Dermatol. 19:e323–e325. 2010. View Article : Google Scholar : PubMed/NCBI
23	Dengjel J, Schoor O, Fischer R, et al: Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci USA. 102:7922–7927. 2005.PubMed/NCBI
24	Lleo A, Invernizzi P, Selmi C, et al: Autophagy: highlighting a novel player in the autoimmunity scenario. J Autoimmun. 29:61–68. 2007. View Article : Google Scholar : PubMed/NCBI