J Korean Med Sci.  2016 Oct;31(10):1566-1570. 10.3346/jkms.2016.31.10.1566.

Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study

Affiliations
  • 1Division of Rheumatology, Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
  • 2Department of Rheumatology, Chonnam National University Medical School, Gwangju, Korea.
  • 3Department of Internal Medicine, Pohang Saint Mary's Hospital, Pohang, Korea.
  • 4Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
  • 5Department of Pathology, School of Medicine, Wonkwang University, Iksan, Korea.
  • 6Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Korea. kimsk714@cu.ac.kr

Abstract

The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.

Keyword

Gout; Polymorphism; P2X7R; CARD8; Inflammasome

MeSH Terms

Adult
Age of Onset
Asian Continental Ancestry Group/*genetics
Body Mass Index
CARD Signaling Adaptor Proteins/*genetics
Case-Control Studies
Disease Susceptibility
Gene Frequency
Genotype
Gout/*genetics/pathology
Humans
Logistic Models
Male
Middle Aged
Neoplasm Proteins/*genetics
Odds Ratio
Polymorphism, Single Nucleotide
Receptors, Purinergic P2X7/*genetics
Republic of Korea
Risk Factors
Uric Acid/blood
CARD Signaling Adaptor Proteins
Neoplasm Proteins
Receptors, Purinergic P2X7
Uric Acid

Reference

1. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440:237–241.
2. Choe JY, Jung HY, Park KY, Kim SK. Enhanced p62 expression through impaired proteasomal degradation is involved in caspase-1 activation in monosodium urate crystal-induced interleukin-1b expression. Rheumatology (Oxford). 2014; 53:1043–1053.
3. Kahlenberg JM, Lundberg KC, Kertesy SB, Qu Y, Dubyak GR. Potentiation of caspase-1 activation by the P2X7 receptor is dependent on TLR signals and requires NF-kappaB-driven protein synthesis. J Immunol. 2005; 175:7611–7622.
4. Ferrari D, Pizzirani C, Adinolfi E, Lemoli RM, Curti A, Idzko M, Panther E, Di Virgilio F. The P2X7 receptor: a key player in IL-1 processing and release. J Immunol. 2006; 176:3877–3883.
5. Gong QY, Chen Y. Correlation between P2X7 receptor gene polymorphisms and gout. Rheumatol Int. 2015; 35:1307–1310.
6. Chen Y, Ren X, Li C, Xing S, Fu Z, Yuan Y, Wang R, Wang Y, Lv W. CARD8 rs2043211 polymorphism is associated with gout in a Chinese male population. Cell Physiol Biochem. 2015; 35:1394–1400.
7. McKinney C, Stamp LK, Dalbeth N, Topless RK, Day RO, Kannangara DR, Williams KM, Janssen M, Jansen TL, Joosten LA, et al. Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout. Arthritis Res Ther. 2015; 17:288.
8. Kastbom A, Johansson M, Verma D, Söderkvist P, Rantapää-Dahlqvist S. CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid arthritis. Ann Rheum Dis. 2010; 69:723–726.
9. Yang SK, Kim H, Hong M, Lim J, Choi E, Ye BD, Park SK, Song K. Association of CARD8 with inflammatory bowel disease in Koreans. J Hum Genet. 2011; 56:217–223.
10. Gu BJ, Zhang W, Worthington RA, Sluyter R, Dao-Ung P, Petrou S, Barden JA, Wiley JS. Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor. J Biol Chem. 2001; 276:11135–11142.
11. Wesselius A, Bours MJ, Arts IC, Theunisz EH, Geusens P, Dagnelie PC. The P2X(7) loss-of-function Glu496Ala polymorphism affects ex vivo cytokine release and protects against the cytotoxic effects of high ATP-levels. BMC Immunol. 2012; 13:64.
12. Al-Shukaili A, Al-Kaabi J, Hassan B, Al-Araimi T, Al-Tobi M, Al-Kindi M, Al-Maniri A, Al-Gheilani A, Al-Ansari A. P2X7 receptor gene polymorphism analysis in rheumatoid arthritis. Int J Immunogenet. 2011; 38:389–396.
13. Chen GM, Feng CC, Ye QL, Tao JH, Li R, Peng H, Zhou M, Leng RX, Li J, Cen H, et al. Association of P2X7R gene polymorphisms with systemic lupus erythematosus in a Chinese population. Mutagenesis. 2013; 28:351–355.
14. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yü TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977; 20:895–900.
15. Al-Mohaya MA, Al-Harthi F, Arfin M, Al-Asmari A. TNF-α, TNF-β and IL-10 gene polymorphism and association with oral lichen planus risk in Saudi patients. J Appl Oral Sci. 2015; 23:295–301.
16. Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol. 2009; 27:229–265.
17. Stokes L, Fuller SJ, Sluyter R, Skarratt KK, Gu BJ, Wiley JS. Two haplotypes of the P2X(7) receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1beta secretion. FASEB J. 2010; 24:2916–2927.
18. Tao JH, Zhang Y, Li XP. P2X7R: a potential key regulator of acute gouty arthritis. Semin Arthritis Rheum. 2013; 43:376–380.
19. Gadeock S, Pupovac A, Sluyter V, Spildrejorde M, Sluyter R. P2X7 receptor activation mediates organic cation uptake into human myeloid leukaemic KG-1 cells. Purinergic Signal. 2012; 8:669–676.
20. Bouchier-Hayes L, Conroy H, Egan H, Adrain C, Creagh EM, MacFarlane M, Martin SJ. CARDINAL, a novel caspase recruitment domain protein, is an inhibitor of multiple NF- kappa B activation pathways. J Biol Chem. 2001; 276:44069–44077.
21. Razmara M, Srinivasula SM, Wang L, Poyet JL, Geddes BJ, DiStefano PS, Bertin J, Alnemri ES. CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis. J Biol Chem. 2002; 277:13952–13958.
22. Fontalba A, Martinez-Taboada V, Gutierrez O, Pipaon C, Benito N, Balsa A, Blanco R, Fernandez-Luna JL. Deficiency of the NF-kappaB inhibitor caspase activating and recruitment domain 8 in patients with rheumatoid arthritis is associated with disease severity. J Immunol. 2007; 179:4867–4873.
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr