DOI QR코드

DOI QR Code

Polymorphism of NLRP3 Gene and Association with Susceptibility to Digestive Disorders in Rabbit

  • Yang, Yu (Institute of Animal Genetics and Breeding, Sichuan Agricultural University) ;
  • Zhang, Gong-Wei (Institute of Animal Genetics and Breeding, Sichuan Agricultural University) ;
  • Chen, Shi-Yi (Institute of Animal Genetics and Breeding, Sichuan Agricultural University) ;
  • Peng, Jin (Institute of Animal Genetics and Breeding, Sichuan Agricultural University) ;
  • Lai, Song-Jia (Institute of Animal Genetics and Breeding, Sichuan Agricultural University)
  • Received : 2012.09.19
  • Accepted : 2012.10.25
  • Published : 2013.04.01

Abstract

NLR family pyrin domain containing 3 (NLRP3) is a key component of the inflammasome, whose assembly is a crucial part of the innate immune response. The aim of the present study was to evaluate the association between exon 3 polymorphisms of NLRP3 and the susceptibility to digestive disorders in rabbits. In total, five coding single-nucleotide polymorphisms (cSNPs) were identified; all of which are synonymous. Among them, c.456 C> and c.594 G> were further genotyped for association analysis based on case-control design (n =162 vs n =102). Meanwhile, growing rabbits were experimentally induced to digestive disorders by feeding a fiber-deficient diet, subsequently they were subjected to mRNA expression analysis. Association analysis revealed that haplotype H1 (the two cSNPs: GT) played a potential protective role against digestive disorders (p<0.001). The expression of NLRP3 in the group $H1HX_1$ ($H1HX_1$ is composed of H1H1, H1H3 and H1H4) was the lowest among four groups which were classified by different types of diplotypes. Those results suggested that the NLRP3 gene was significantly associated with susceptibility to digestive disorders in rabbit.

Keywords

References

  1. Agostini, L., F. Martinon, K. Burns, M. F. McDermott, P. N. Hawkins and J. Tschopp. 2004. NALP3 forms an IL-1 [beta]-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20:319-325. https://doi.org/10.1016/S1074-7613(04)00046-9
  2. Andoh, A., Y. Benno, O. Kanauchi and Y. Fujiyama. 2009. Recent advances in molecular approaches to gut microbiota in inflammatory bowel disease. Curr. Pharm. Des. 15:2066-2073. https://doi.org/10.2174/138161209788489186
  3. Bauer, C., P. Duewell, C. Mayer, H. A. Lehr, K. A. Fitzgerald, M. Dauer, J. Tschopp, S. Endres, E. Latz and M. Schnurr. 2010. Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut. 59:1192-1199. https://doi.org/10.1136/gut.2009.197822
  4. Bennegadi, N., T. Gidenne and D. Licois. 2001. Impact of fibre deficiency and sanitary status on non-specific enteropathy of the growing rabbit. Anim. Res.50:401-413. https://doi.org/10.1051/animres:2001135
  5. Comeron, J. M. 2004. Selective and mutational patterns associated with gene expression in humans: Influences on synonymous composition and intron presence. Genetics 167:1293-1304. https://doi.org/10.1534/genetics.104.026351
  6. Cummings, J., R. Cooney, G. Clarke, J. Beckly, A. Geremia, S. Pathan, L. Hancock, C. Guo, L. Cardon and D. Jewell. 2010. The genetics of NOD?like receptors in Crohn's disease. Tissue Antigens 76:48-56.
  7. Dowds, T. A., J. Masumoto, L. Zhu, N. Inohara and G. Nunez. 2004. Cryopyrin-induced interleukin $1\beta$ secretion in monocytic cells. J. Biol. Chem. 279:21924-21928. https://doi.org/10.1074/jbc.M401178200
  8. Dupaul-Chicoine, J., G. Yeretssian, K. Doiron, K. S. B. Bergstrom, C. R. McIntire, P. M. LeBlanc, C. Meunier, C. Turbide, P. Gros and N. Beauchemin. 2010. Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. Immunity 32:367-378. https://doi.org/10.1016/j.immuni.2010.02.012
  9. Eady, S., H. Garreau and A. Gilmour. 2007. Heritability of resistance to bacterial infection in meat rabbits. Livest. Sci. 112:90-98. https://doi.org/10.1016/j.livsci.2007.01.158
  10. Garreau, H., S. Eady, J. Hurtaud and A. Legarra. 2008. Genetic parameters of production traits and resistance to digestive disorders in a commercial rabbit population. Proc. 9th World Rabbit Congr. 10-13.
  11. Gidenne, T., V. Pinheiro and L. Falcao e Cunha. 2000. A comprehensive approach of the rabbit digestion: consequences of a reduction in dietary fibre supply. Livest. Prod. Sci. 64: 225-237. https://doi.org/10.1016/S0301-6226(99)00141-4
  12. Goymer, P. 2007. Synonymous mutations break their silence. Nat. Rev. Genet. 8:92.
  13. Hirota, S. A., J. Ng, A. Lueng, M. Khajah, K. Parhar, Y. Li, V. Lam, M. S. Potentier, K. Ng and M. Bawa. 2011. NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. Inflamm. Bowel Dis. 17:1359-1372. https://doi.org/10.1002/ibd.21478
  14. Kanneganti, T. D., M. Lamkanfi and G. Nunez. 2007. Intracellular NOD-like receptors in host defense and disease. Immunity 27: 549-559. https://doi.org/10.1016/j.immuni.2007.10.002
  15. Kastbom, A., D. Verma, P. Eriksson, T. Skogh, G. Wingren and P. Soderkvist. 2008. Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (the Swedish TIRA project). Rheumatology 47:415-417.
  16. Lamkanfi, M., T. D. Kanneganti, L. Franchi and G. Nunez. 2007. Caspase-1 inflammasomes in infection and inflammation. J. Leukoc. Biol. 82:220-225. https://doi.org/10.1189/jlb.1206756
  17. Li, Z., Z. Zhang, Z. He, W. Tang, T. Li, Z. Zeng, L. He and Y. Shi. 2009. A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis (http://analysis. bio-x. cn). Cell Res. 19:519-523. https://doi.org/10.1038/cr.2009.33
  18. Liu, H. and Y. Hu. 2010. Hardy-Weinberg equilibrium in genetic epidemiology. Zhong nan da xue xue bao. Yi xue ban= Journal of Central South University. Med Sci. 35:90-93.
  19. Mariathasan, S. and D. M. Monack. 2007. Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat. Rev. Immunol. 7:31-40. https://doi.org/10.1038/nri1997
  20. Martinon, F. and J. Tschopp. 2006. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ. 14:10-22.
  21. Ott, J. 2004. Association of genetic loci. Neurology 63:955-958. https://doi.org/10.1212/WNL.63.6.955
  22. Petrilli, V., C. Dostert, D. A. Muruve and J. Tschopp. 2007. The inflammasome: a danger sensing complex triggering innate immunity. Curr. Opin. Immunol. 19:615-622. https://doi.org/10.1016/j.coi.2007.09.002
  23. Roberts, R., R. Topless, A. Phipps-Green, R. Gearry, M. Barclay and T. Merriman. 2010. Evidence of interaction of CARD8 rs2043211 with NALP3 rs35829419 in Crohn's disease. Genes Immun. 11:351-356. https://doi.org/10.1038/gene.2010.11
  24. Rosell, J. 2003. Health status of commercial rabbitries in the Iberian peninsula. A practitioner's study during 2002. World Rabbit Sci. 11:157-169.
  25. Royet, J. and J. M. Reichhart. 2003. Detection of peptidoglycans by NOD proteins. Trends Cell Biol.13(12): 610-614. https://doi.org/10.1016/j.tcb.2003.10.003
  26. Sauna, Z. E. and C. Kimchi-Sarfaty. 2011. Understanding the contribution of synonymous mutations to human disease. Nat. Rev. Genet. 12:683-691.
  27. Schoultz, I., D. Verma, J. Halfvarsson, L. Torkvist, M. Fredrikson, U. Sjoqvist, M. Lordal, C. Tysk, M. Lerm and P. Soderkvist. 2009. Combined polymorphisms in genes encoding the inflammasome components NALP3 and CARD8 confer susceptibility to Crohn's disease in Swedish men. Am J Gastroenterol. 104:1180-1188. https://doi.org/10.1038/ajg.2009.29
  28. Sharp, P. M. and W. H. Li. 1986. Codon usage in regulatory genes in Escherichia coli does not reflect selection for 'rare'codons. Nucleic Acids Res. 14:7737-7749. https://doi.org/10.1093/nar/14.19.7737
  29. Stephens, M., N. J. Smith and P. Donnelly. 2001. A new statistical method for haplotype reconstruction from population data. Am. J. Hum. Genet. 68:978-989. https://doi.org/10.1086/319501
  30. Ting, J. P. Y., D. L. Kastner and H. M. Hoffman. 2006. CATERPILLERs, pyrin and hereditary immunological disorders. Nat. Rev. Immunol. 6:183-195. https://doi.org/10.1038/nri1788
  31. Vandesompele, J., K. De Preter, F. Pattyn, B. Poppe, N. Van Roy, A. De Paepe and F. Speleman. 2002. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3:research0034.
  32. Villani, A. C., M. Lemire, G. Fortin, E. Louis, M. S. Silverberg, C. Collette, N. Baba, C. Libioulle, J. Belaiche and A. Bitton. 2008. Common variants in the NLRP3 region contribute to Crohn's disease susceptibility. Nat. Genet. 41:71-76.
  33. Zhang, G. W., H. Z. Wang, S. Y. Chen, Z. C. Li, W. X. Zhang and S. J. Lai. 2011. A reduced incidence of digestive disorders in rabbits is associated with allelic diversity at the TLR4 locus. Vet. Immunol. Immunopathol. 144:482-486. https://doi.org/10.1016/j.vetimm.2011.08.009
  34. Zheng, S. L., K. Augustsson-Balter, B. Chang, M. Hedelin, L. Li, H. O. Adami, J. Bensen, G. Li, J. E. Johnasson and A. R. Turner. 2004. Sequence variants of toll-Like receptor 4 are associated with prostate cancer risk. Cancer Res. 64:2918. https://doi.org/10.1158/0008-5472.CAN-03-3280

Cited by

  1. A synonymous mutation of uncoupling protein 2 (UCP2) gene is associated with growth performance, carcass characteristics and meat quality in rabbits vol.58, pp.1, 2016, https://doi.org/10.1186/s40781-016-0086-4
  2. Investigation of significant microRNA-mRNA pairs associated with nonspecific digestive disorder in rabbits vol.25, pp.4, 2017, https://doi.org/10.4995/wrs.2017.6839
  3. Disentangling synergistic disease dynamics: Implications for the viral biocontrol of rabbits vol.87, pp.5, 2018, https://doi.org/10.1111/1365-2656.12871
  4. Investigation of genetic susceptibility to nonspecific digestive disorder between TYK2, JAK1, and STAT3 genes in rabbits vol.181, pp.None, 2013, https://doi.org/10.1016/j.livsci.2015.08.014