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Polymorphism, Expression of Natural Resistance-associated Macrophage Protein 1 Encoding Gene (NRAMP1) and Its Association with Immune Traits in Pigs

  • Ding, Xiaoling (College of Animal Science and Technology, Anhui Agricultural University) ;
  • Zhang, Xiaodong (College of Animal Science and Technology, Anhui Agricultural University) ;
  • Yang, Yong (Anhui Antai Pig Breeding Co., LTD.) ;
  • Ding, Yueyun (College of Animal Science and Technology, Anhui Agricultural University) ;
  • Xue, Weiwei (College of Animal Science and Technology, Anhui Agricultural University) ;
  • Meng, Yun (College of Animal Science and Technology, Anhui Agricultural University) ;
  • Zhu, Weihua (College of Animal Science and Technology, Anhui Agricultural University) ;
  • Yin, Zongjun (College of Animal Science and Technology, Anhui Agricultural University)
  • Received : 2014.01.08
  • Accepted : 2014.04.14
  • Published : 2014.08.01

Abstract

Natural resistance-associated macrophage protein 1 encoding gene (NRAMP1) plays an important role in immune response against intracellular pathogens. To evaluate the effects of NRAMP1 gene on immune capacity in pigs, tissue expression of NRAMP1 mRNA was observed by real time quantitative polymerase chain reaction (PCR), and the results revealed NRAMP1 expressed widely in nine tissues. One single nucleotide polymorphism (SNP) (ENSSSCG00000025058: g.130 C>T) in exon1 and one SNP (ENSSSCG00000025058: g.657 A>G) in intron1 region of porcine NRAMP1 gene were demonstrated by DNA sequencing and PCR-RFLP analysis. A further analysis of SNP genotypes associated with immune traits including contain of white blood cell (WBC), granulocyte, lymphocyte, monocyte (MO), rate of cytotoxin in monocyte (MC) and $CD4^-CD8^+$ T lymphocyte subpopulations in blood was carried out in four pig populations including Large White and three Chinese indigenous breeds (Wannan Black, Huai pig and Wei pig). The results showed that the SNP (ENSSSCG00000025058: g.130 C>T) was significantly associated with level of WBC % (p = 0.031), MO% (p = 0.024), MC% (p = 0.013) and $CD4^-CD8^+$ T lymphocyte (p = 0.023). The other SNP (ENSSSCG00000025058: g.657 A>G) was significantly associated with the level of MO% (p = 0.012), MC% (p = 0.019) and $CD4^-CD8^+$ T lymphocyte (p = 0.037). These results indicate that the NRAMP1 gene can be regarded as a molecular marker for genetic selection of disease susceptibility in pig breeding.

Keywords

Pig;Natural Resistance-associated Macrophage Protein 1 (NRAMP1);Polymorphism;Expression;Association

References

  1. Vidal, S. M., D. Malo, K. Vogan, E. Skamene, and P. Gros. 1993. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73:469-485. https://doi.org/10.1016/0092-8674(93)90135-D
  2. Wu, H., D. Cheng, and L. Wang. 2008. Association of polymorphisms of Nramp1 gene with immune function and production performance of Large White pig. J. Genet. Genomics 35:91-95. https://doi.org/10.1016/S1673-8527(08)60014-4
  3. Wyllie, S., P. Seu, and J. A. Goss. 2002. The natural resistanceassociated macrophage protein 1 NRAMP1 (formerly Nramp1) and iron metabolism in macrophages. Microbes Infect. 4:351-359. https://doi.org/10.1016/S1286-4579(02)01548-4
  4. Yang, J. H., K. Downes, J. M. Howson, S. Nutland, H. E. Stevens, N. M. Walker, and J. A. Todd. 2011. Evidence of association with type 1 diabetes in the SLC11A1 gene region. BMC Med. Genet. 12:59.
  5. Liu, Y., X. T. Qiu, J. J. Xu, F. Hu, Y. H. Li, H. J. Li, Y. F. Gong, and Q. Zhang. 2011. Association analysis between the polymorphism of the SLC11A1 gene and immune response traits in pigs. Asian J. Anim. Vet. Adv. 6:580-586. https://doi.org/10.3923/ajava.2011.580.586
  6. Meilang, Q., Y. Zhang, J. Zhang, Y. Zhao, C. Tian, J. Huang, and H. Fan. 2012. Polymorphisms in the SLC11A1 gene and tuberculosis risk: a meta-analysis update. Int. J. Tuberc. Lung Dis. 16:437-446. https://doi.org/10.5588/ijtld.10.0743
  7. Pauly, T., K. Elbers, M. Konig, T. Lengsfeld, A. Saalmuller, and H. J. Thiel. 1995. Classical swine fever virus-specific cytotoxic T lymphocytes and identification of a T cell epitope. J. Gen. Virol. 76:3039-3049. https://doi.org/10.1099/0022-1317-76-12-3039
  8. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor Laboratory Press, New York, USA.
  9. Sapkota, B. R., M. Hijikata, I. Matsushita, G. Tanaka, R. Ieki, N. Kobayashi, E. Toyota, H. Nagai, A. Kurashima, K. Tokunaga, and N. Keicho. 2012. Association of SLC11A1 (NRAMP1) polymorphisms with pulmonary Mycobacterium avium complex infection. Hum. Immunol. 73:529-536. https://doi.org/10.1016/j.humimm.2012.02.008
  10. Smit, J. J., G. Folkerts, and F. P. Nijkamp. 2004. Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis. Trends Immunol. 25:342-347. https://doi.org/10.1016/j.it.2004.04.010
  11. Tanaka, G., J. Shojima, I. Matsushita, H. Nagai, A. Kurashima, K. Nakata, E. Toyota, N. Kobayashi, K. Kudo, and N. Keicho. 2007. Pulmonary Mycobacterium avium complex infection: Association with NRAMP1 polymorphisms. Eur. Respir. J. 30: 90-96. https://doi.org/10.1183/09031936.00042506
  12. Tuggle, C. K., C. B. Schmitz, and D. Gingerich-Feil. 1997. Rapid communication: cloning of a pig full-length NRAMP1 cDNA. J. Anim. Sci. 75:277.
  13. Tuggle, C. K., L. Marklund, T. J. Stabel, M. A. Mellencamp, and A. Stumbaugh. 2005. Genetic markers for screening animals for improved disease resistance (NRAMP). United States Patent, Patent No. :US 6,844,159 B2.
  14. Capon, F., M. H. Allen, M. Ameen, A. D. Burden, D. Tillman, J. N. Barkerand, and R. C. Trembath. 2004. A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups. Hum. Mol. Genet. 13:2361-2368. https://doi.org/10.1093/hmg/ddh273
  15. Courville, P., R. Chaloupka, and M. F. Cellier. 2006. Recent progress in structure-function analyses of Nramp protondependent metal-ion transporters. Biochem. Cell Biol. 84:960-978. https://doi.org/10.1139/o06-193
  16. Crawley, A. M., B. Mallard, and B. N. Wilkie. 2005. Genetic selection for high and low immune response in pigs: Effects on immunoglobulin isotype expression. Vet. Immunol. Immunopathol. 108:71-76. https://doi.org/10.1016/j.vetimm.2005.07.006
  17. Gazouli, M., V. Atsaves, G. Mantzaris, M. Economou, G. Nasioulas, K. Evangelou, A. J. Archimandritis, and N. P. Anagnou. 2008. Role of functional polymorphisms of NRAMP1 gene for the development of Crohn's disease. Inflamm. Bowel. Dis. 14:1323-1330. https://doi.org/10.1002/ibd.20488
  18. Hellemans, J., G. Mortier, A. De Paepe, F. Speleman, and J. Vandesompele. 2007. qBase relative quantification framework and software for management and automated analysis of realtime quantitative PCR data. Genome Biol. 8:R19. https://doi.org/10.1186/gb-2007-8-2-r19
  19. He, X. M., M. X. Fang, Z. T. Zhang, Y. S. Hu, X. Z. Jia, D. L. He, S. D. Liang, Q. H. Nie, and X. Q. Zhang. 2013. Characterization of chicken natural resistance-associated macrophage protein encoding genes (Nramp1 and Nramp2) and association with salmonellosis resistance. Genet. Mol. Res. 12:618-630. https://doi.org/10.4238/2013.January.30.5
  20. Hedges, J. F., E. Kimmel, D. T. Snyder, M. Jerome, and M. A. Jutila. 2013. Solute carrier 11A1 is expressed by innate lymphocytes and augments their activation. J. Immunol. 190:4263-4273. https://doi.org/10.4049/jimmunol.1200732
  21. Kimchi-Sarfaty, C., J. M. Oh, I. W. Kim, Z. E. Sauna, A. M. Calcagno, S. V. Ambudkar, and M. M. Gottesman. 2007. A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science 315(5811):525-528. https://doi.org/10.1126/science.1135308
  22. Ates, O., L. Dalyan, B. Musellim, G. Hatemi, H. Turker, G. Ongen, V. Hamuryudan, and A. Topal-Sarikaya. 2009. NRAMP1 (SLC11A1) gene polymorphisms that correlate with autoimmune versus infectious disease susceptibility in tuberculosis and rheumatoid arthritis. Int. J. Immunogenet. 36: 15-19. https://doi.org/10.1111/j.1744-313X.2008.00814.x
  23. Blackwell, J. M., S. Searle, T. Goswami, and E. N. Miller. 2000. Understanding the multiple functions of Nramp1. Microbes Infect. 2:317-321. https://doi.org/10.1016/S1286-4579(00)00295-1
  24. Blackwell, J. M., S. Searle, H. Mohamed, and J. K. White. 2003. Divalent cation transport and susceptibility to infectious and autoimmune disease: Continuation of the Ity/Lsh/Bcg/Nramp1/ Slc11a1 gene story. Immunol. Lett. 85:197-203. https://doi.org/10.1016/S0165-2478(02)00231-6
  25. Canonne-Hergaux, F., S. Gruenheid, P. Ponka, and P. Gros. 1999. Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood 93:4406-4417.

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