18Feb 2017

THE GENETICS OF SYSTEMIC LUPUSERYTHEMATOSUSIN SAUDI ARABIA

  • Department of Pathology, School of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia.
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Systemic Lupus Erythematosus (SLE) is a complex multisystem autoimmune disorder. It is characterized by the production of autoantibodies that react against its own tissues, which may lead to immune-complex mediated end organ involvement. There are more than 30 genetic loci in different ethnic backgrounds that have been associated with the risk of developing this disease. The high level of consanguinityin the Saudi population is a risk factor for developing the disease. On the other hand, it provides an opportunity to identify the genetic variations that are associated with the disease. Applying Genome Wide Association Studies (GWAS) and exome sequencing would help to identify these variations. This review provides an opportunity to outline the genetics of Systemic Lupus Erythematosus in the Saudi population.

  1. Al Arfaj, A. S., & Khalil, N. (2009). Clinical and immunological manifestations in 624 SLE patients in Saudi Arabia. Lupus, 18(5), 465-473. doi:10.1177/0961203308100660
  2. al-Abdulkareem, A. A., & Ballal, S. G. (1998). Consanguineous marriage in an urban area of Saudi Arabia: rates and adverse health effects on the offspring. J Community Health, 23(1), 75-83.
  3. Al-Mayouf, S. M., Sunker, A., Abdwani, R., Abrawi, S. A., Almurshedi, F., Alhashmi, N., . . . Alkuraya, F. S. (2011). Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat Genet, 43(12), 1186-1188. doi:10.1038/ng.975
  4. Alarcon, G. S., Friedman, A. W., Straaton, K. V., Moulds, J. M., Lisse, J., Bastian, H. M., . . . Reveille, J. D. (1999). Systemic lupus erythematosus in three ethnic groups: III. A comparison of characteristics early in the natural history of the LUMINA cohort. LUpus in MInority populations: NAture vs. Nurture. Lupus, 8(3), 197-209.
  5. Alarcon, G. S., McGwin, G., Jr., Petri, M., Reveille, J. D., Ramsey-Goldman, R., & Kimberly, R. P. (2002). Baseline characteristics of a multiethnic lupus cohort: PROFILE. Lupus, 11(2), 95-101.
  6. Bittles, A. H., & Black, M. L. (2010). Evolution in health and medicine Sackler colloquium: Consanguinity, human evolution, and complex diseases. Proc Natl Acad Sci U S A, 107 Suppl 1, 1779-1786. doi:10.1073/pnas.0906079106
  7. Borchers, A. T., Naguwa, S. M., Shoenfeld, Y., & Gershwin, M. E. (2010). The geoepidemiology of systemic lupus erythematosus. Autoimmun Rev, 9(5), A277-287. doi:10.1016/j.autrev.2009.12.008
  8. Cervera, R., Khamashta, M. A., Font, J., Sebastiani, G. D., Gil, A., Lavilla, P., . . . Hughes, G. R. (1999). Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore), 78(3), 167-175.
  9. Chung, S. A., Tian, C., Taylor, K. E., Lee, A. T., Ortmann, W. A., Hom, G., . . . Criswell, L. A. (2009). European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus. Arthritis Rheum, 60(8), 2448-2456. doi:10.1002/art.24707
  10. Do, R., Kathiresan, S., & Abecasis, G. R. (2012). Exome sequencing and complex disease: practical aspects of rare variant association studies. Hum Mol Genet, 21(R1), R1-9. doi:10.1093/hmg/dds387
  11. El-Mouzan, M. I., Al-Salloum, A. A., Al-Herbish, A. S., Qurachi, M. M., & Al-Omar, A. A. (2007). Regional variations in the prevalence of consanguinity in Saudi Arabia. Saudi Med J, 28(12), 1881-1884.
  12. Fernandez, M., Alarcon, G. S., Calvo-Alen, J., Andrade, R., McGwin, G., Jr., Vila, L. M., & Reveille, J. D. (2007). A multiethnic, multicenter cohort of patients with systemic lupus erythematosus (SLE) as a model for the study of ethnic disparities in SLE. Arthritis Rheum, 57(4), 576-584. doi:10.1002/art.22672
  13. Fessel, W. J. (1974). Systemic lupus erythematosus in the community. Incidence, prevalence, outcome, and first symptoms; the high prevalence in black women. Arch Intern Med, 134(6), 1027-1035.
  14. Gateva, V., Sandling, J. K., Hom, G., Taylor, K. E., Chung, S. A., Sun, X., . . . Graham, R. R. (2009). A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet, 41(11), 1228-1233. doi:10.1038/ng.468
  15. Graham, R. R., Kozyrev, S. V., Baechler, E. C., Reddy, M. V., Plenge, R. M., Bauer, J. W., . . . Alarcon-Riquelme, M. E. (2006). A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet, 38(5), 550-555. doi:10.1038/ng1782
  16. Guerra, S. G., Vyse, T. J., & Cunninghame Graham, D. S. (2012). The genetics of lupus: a functional perspective. Arthritis Res Ther, 14(3), 211. doi:10.1186/ar3844
  17. Guthridge, J. M., Clark, D. N., Templeton, A., Dominguez, N., Lu, R., Vidal, G. S., . . . Poole, B. D. (2012). Effects of IRF5 lupus risk haplotype on pathways predicted to influence B cell functions. J Biomed Biotechnol, 2012, 594056. doi:10.1155/2012/594056
  18. Hannema, A. J., Kluin-Nelemans, J. C., Hack, C. E., Eerenberg-Belmer, A. J., Mallee, C., & van Helden, H. P. (1984). SLE like syndrome and functional deficiency of C1q in members of a large family. Clin Exp Immunol, 55(1), 106-114.
  19. Harley, J. B., Alarcon-Riquelme, M. E., Criswell, L. A., Jacob, C. O., Kimberly, R. P., Moser, K. L., . . . Kelly, J. A. (2008). Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet, 40(2), 204-210. doi:10.1038/ng.81
  20. Heller, T., Ahmed, M., Siddiqqi, A., Wallrauch, C., & Bahlas, S. (2007). Systemic lupus erythematosus in Saudi Arabia: morbidity and mortality in a multiethnic population. Lupus, 16(11), 908-914. doi:10.1177/0961203307081112
  21. Hersh, A. O., Alarcon, G. S., Bonetto, C., Pernus, Y. B., Kucuku, M., Santuccio, C., . . . Bonhoeffer, J. (2016). Systemic Lupus Erythematosus: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine, 34(51), 6572-6581. doi:10.1016/j.vaccine.2016.09.031
  22. Hom, G., Graham, R. R., Modrek, B., Taylor, K. E., Ortmann, W., Garnier, S., . . . Behrens, T. W. (2008). Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med, 358(9), 900-909. doi:10.1056/NEJMoa0707865
  23. Hunter-Zinck, H., Musharoff, S., Salit, J., Al-Ali, K. A., Chouchane, L., Gohar, A., . . . Clark, A. G. (2010). Population genetic structure of the people of Qatar. Am J Hum Genet, 87(1), 17-25. doi:10.1016/j.ajhg.2010.05.018
  24. Iwamoto, T., & Niewold, T. B. (2016). Genetics of human lupus nephritis. Clin Immunol. doi:10.1016/j.clim.2016.09.012
  25. Lee-Kirsch, M. A., Gong, M., Chowdhury, D., Senenko, L., Engel, K., Lee, Y. A., . . . Hubner, N. (2007). Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet, 39(9), 1065-1067. doi:10.1038/ng2091
  26. Lopez, P., Mozo, L., Gutierrez, C., & Suarez, A. (2003). Epidemiology of systemic lupus erythematosus in a northern Spanish population: gender and age influence on immunological features. Lupus, 12(11), 860-865.
  27. Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., . . . Visscher, P. M. (2009). Finding the missing heritability of complex diseases. Nature, 461(7265), 747-753. doi:10.1038/nature08494
  28. Meyer, O., Hauptmann, G., Tappeiner, G., Ochs, H. D., & Mascart-Lemone, F. (1985). Genetic deficiency of C4, C2 or C1q and lupus syndromes. Association with anti-Ro (SS-A) antibodies. Clin Exp Immunol, 62(3), 678-684.
  29. Mohammad, T., Xue, Y., Evison, M., & Tyler-Smith, C. (2009). Genetic structure of nomadic Bedouin from Kuwait. Heredity (Edinb), 103(5), 425-433. doi:10.1038/hdy.2009.72
  30. Mohan, C., & Putterman, C. (2015). Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis. Nat Rev Nephrol, 11(6), 329-341. doi:10.1038/nrneph.2015.33
  31. Moser, K. L., Kelly, J. A., Lessard, C. J., & Harley, J. B. (2009). Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun, 10(5), 373-379. doi:10.1038/gene.2009.39
  32. Moulton, V. R., Lo, M. S., & Tsokos, G. C. (2012). Methods and protocols to study T cell signaling abnormalities in human systemic lupus erythematosus. Methods Mol Biol, 900, 25-60. doi:10.1007/978-1-60761-720-4_3
  33. Nassir, R., Kosoy, R., Tian, C., White, P. A., Butler, L. M., Silva, G., . . . Seldin, M. F. (2009). An ancestry informative marker set for determining continental origin: validation and extension using human genome diversity panels. BMC Genet, 10, 39. doi:10.1186/1471-2156-10-39
  34. O'Neill, S., & Cervera, R. (2010). Systemic lupus erythematosus. Best Pract Res Clin Rheumatol, 24(6), 841-855. doi:10.1016/j.berh.2010.10.006
  35. Pons-Estel, G. J., Alarcon, G. S., Scofield, L., Reinlib, L., & Cooper, G. S. (2010). Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum, 39(4), 257-268. doi:10.1016/j.semarthrit.2008.10.007
  36. Qari, F. A. (2002). Clinical pattern of systemic lupus erythematosus in Western Saudi Arabia. Saudi Med J, 23(10), 1247-1250.
  37. Ramos, P. S., Criswell, L. A., Moser, K. L., Comeau, M. E., Williams, A. H., Pajewski, N. M., . . . Langefeld, C. D. (2011). A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap. PLoS Genet, 7(12), e1002406. doi:10.1371/journal.pgen.1002406
  38. Remmers, E. F., Plenge, R. M., Lee, A. T., Graham, R. R., Hom, G., Behrens, T. W., . . . Gregersen, P. K. (2007). STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med, 357(10), 977-986. doi:10.1056/NEJMoa073003
  39. Richman, I. B., Chung, S. A., Taylor, K. E., Kosoy, R., Tian, C., Ortmann, W. A., . . . Criswell, L. A. (2010). European population substructure correlates with systemic lupus erythematosus endophenotypes in North Americans of European descent. Genes Immun, 11(6), 515-521. doi:10.1038/gene.2009.80
  40. Richman, I. B., Taylor, K. E., Chung, S. A., Trupin, L., Petri, M., Yelin, E., . . . Criswell, L. A. (2012). European genetic ancestry is associated with a decreased risk of lupus nephritis. Arthritis Rheum, 64(10), 3374-3382. doi:10.1002/art.34567
  41. Rudan, I., Rudan, D., Campbell, H., Carothers, A., Wright, A., Smolej-Narancic, N., . . . Rudan, P. (2003). Inbreeding and risk of late onset complex disease. J Med Genet, 40(12), 925-932.
  42. Rynes, R. I. (1982). Inherited complement deficiency states and SLE. Clin Rheum Dis, 8(1), 29-47.
  43. Sanchez, E., Rasmussen, A., Riba, L., Acevedo-Vasquez, E., Kelly, J. A., Langefeld, C. D., . . . Alarcon-Riquelme, M. E. (2012). Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations. Arthritis Rheum, 64(11), 3687-3694. doi:10.1002/art.34650
  44. Shin, M. S., Lee, N., & Kang, I. (2011). Effector T-cell subsets in systemic lupus erythematosus: update focusing on Th17 cells. Curr Opin Rheumatol, 23(5), 444-448. doi:10.1097/BOR.0b013e328349a255
  45. Smith, P. P., & Gordon, C. (2010). Systemic lupus erythematosus: clinical presentations. Autoimmun Rev, 10(1), 43-45. doi:10.1016/j.autrev.2010.08.016
  46. Tian, C., Kosoy, R., Nassir, R., Lee, A., Villoslada, P., Klareskog, L., . . . Seldin, M. F. (2009). European population genetic substructure: further definition of ancestry informative markers for distinguishing among diverse European ethnic groups. Mol Med, 15(11-12), 371-383. doi:10.2119/molmed.2009.00094
  47. Tsokos, G. C. (2011). Systemic lupus erythematosus. N Engl J Med, 365(22), 2110-2121. doi:10.1056/NEJMra1100359
  48. Williams, E. M., Bruner, L., Adkins, A., Vrana, C., Logan, A., Kamen, D., & Oates, J. C. (2016). I too, am America: a review of research on systemic lupus erythematosus in African-Americans. Lupus Sci Med, 3(1), e000144. doi:10.1136/lupus-2015-000144
  49. Wu, J., Wilson, J., He, J., Xiang, L., Schur, P. H., & Mountz, J. D. (1996). Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease. J Clin Invest, 98(5), 1107-1113. doi:10.1172/jci118892
  50. Yang, W., Shen, N., Ye, D. Q., Liu, Q., Zhang, Y., Qian, X. X., . . . Lau, Y. L. (2010). Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genet, 6(2), e1000841. doi:10.1371/journal.pgen.1000841

[Rami Nassir. (2017); THE GENETICS OF SYSTEMIC LUPUSERYTHEMATOSUSIN SAUDI ARABIA Int. J. of Adv. Res. 5 (Feb). 524-529] (ISSN 2320-5407). www.journalijar.com

Rami Nassir
Assistant Professor in Medical Genetics, Pathology Dept., School of Medicine Umm Al-Qura University

DOI:

Article DOI: 10.21474/IJAR01/3181      
DOI URL: http://dx.doi.org/10.21474/IJAR01/3181

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