medigraphic.com
ISSN 0016-3813 (Print)

2012, Number 4

<< Back Next >>

Gac Med Mex 2012; 148 (4)

Systemic lupus erythematosus: Genomics of the disease

Velázquez-Cruz R, Jiménez-Morales S, Ramírez-Bello J, Aguilar-Delfín I, Salas-Martínez G, Baca RV, Orozco OL

Language: Spanish
References: 76
Page: 371-380
PDF size: 395.20 Kb.


ABSTRACT

Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with multiple autoantigens as targets, resulting in damage to many organs of the body. The disease is more common in females (› 90%) and around 15% of the cases present during childhood.
Systemic lupus erythematosus is a complex disease in which both genetic (susceptibility/protection alleles) and environmental factors (infections, drugs, stress, etc.) contribute to its development.
The current knowledge on genetic factors involved in SLE is based on the results of linkage analyses in multi-case families as well as from case-control or family-based genetic association studies. These types of genetic analyses have contributed to identifying susceptibility genes and constitute the first step towards understanding the molecular mechanisms underlying SLE.
The aim of this review is to provide a current picture of the genes identified as susceptibility factors for SLE, and to highlight the ones described in the Mexican population.


REFERENCES

  1. Collins FS, Brooks LD, Chakravarti A. A DNA polymorphism discovery resource for research on human genetic variation. Genome Res. 1998;8:1229-31.

  2. Seng KC, Seng CK. The success of the genome-wide association approach: a brief story of a long struggle. Eur J Hum Genet. 2008;16:554-64.

  3. Ronaghi M, Langaee T. Single nucleotide polymorphisms: discovery, detection and analysis. Perzonalized medicine. 2005;2:111-25.

  4. Hochberg MC. The epidemiology of systemic lupus erythematosus. En: Wallace DJ, Hahn BH, eds. Dubois’ Lupus Erythematosus. Baltimore: Williams and Wilkins; 1997. p. 49-65.

  5. Stichweh D, Pascual V. Systemic lupus erythematosus in children. An Pediatr. 2005;63:319-27.

  6. Klein-Gitelman M, Reiff A, Silverman ED. Systemic lupus erythematosus in childhood. Rheum Dis Clin North Am. 2002;28:561-77.

  7. Boon SJ, McCurdy D. Childhood systemic lupus erythematosus. Pediatric Ann. 2002;31:407-17.

  8. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.

  9. Kelly JA, Harley JB. The genetics of systemic lupus erythematosus: putting the pieces together. Genes Immun. 2002;3Suppl 1:S71-85.

  10. Freemer MM, King TE Jr, Criswell LA. Association of smoking with ds- DNA autoantibody production in systemic lupus erythematosus. Ann Rheum Dis. 2006;5;581-4.

  11. James JA, Harley JB, Scofield RH. Epstein-Barr virus and systemic lupus erythematosus. Curr Opin Rheumatol. 2006;18:462-7.

  12. Harley IT, Kaufman KM, Langefeld CD, Harley JB, Kelly JA. Genetic susceptibility to SLE: new insights from fine mapping and genome-wide association studies. Nat Rev Genet. 2009;10:285-90.

  13. Alarcón-Segovia D, Alarcón-Riquelme ME, Cardiel MH, et al. Familial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1,177 lupus patients from the GLADEL cohort. Arthritis & Rheum. 2005;52:1138-47.

  14. Wong M, Tsao BP. Current topics in human SLE genetics. Springer Semin Immunol. 2006;28:97-107.

  15. Baca V, Orozco L. La genética de las enfermedades complejas. En: La frontera: genética molecular de la enfermedad. Instituto Politécnico Nacional; 2004. p. 77-91.

  16. Laird NM, Lange C. Family-based designs in the age of large-scale gene-association studies. Nat Rev Genet. 2008;7:385-94.

  17. Sestak AL, Nath SK, Sawalha AH, Harley JB. Current status of lupus genetics. Arthritis Res Ther. 2007;9:210.

  18. Moser KL, Neas BR, Salmon JE, et al. Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees. Proc Natl Acad Sci USA. 1998;95: 14869-74.

  19. Edberg JC, Langefeld CD, Wu J, et al. Genetic linkage and association of Fcgamma receptor IIIA (CD16A) on chromosome 1q23 with human systemic lupus erythematosus. Arthritis Rheum. 2002;46:2132-40.

  20. Prokunina L, Castillejo-López C, Oberg F, et al. A regulatory polymorphism in PDCD1 is associated eith susceptibility to systemic lupus erythematosus in humans. Nat Genet. 2002;32:666-9.

  21. Gray-McGuire C, Moser KL, Gaffney PM, et al. Genome scan of human systemic lupus erythematosus by regression modeling: evidence of linkage and epistasis at 4p16-15.2. Am J Hum Genet. 2000;67:1460-9.

  22. Graham RR, Ortmann WA, Langefeld CD, et al. Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus. Am J Hum Genet. 2002;71:543-53.

  23. Cantor RM, Yuan J, Napier S, et al. Systemic lupus erythematosus genome scan: support for linkage at 1q23, 2q33, 16q12-13, and 17q21-23 and novel evidence at 3p24, 10q23-24, 13q32, and 18q22-23. Arthritis Rheum. 2004;50:3203-10.

  24. Nath SK, Quintero-Del-Rio AI, Kilpatrick J, Feo L, Ballesteros M, Harley JB. Linkage at 12q24 with systemic lupus erythematosus (SLE) is established and confirmed in Hispanic and European American families. Am J Hum Genet. 2004;74:73-82.

  25. Nath SK, Namjou B, Hutchings D, et al. Systemic lupus erythematosus (SLE) and chromosome 16: confirmation of linkage to 16q12-13 and evidence for genetic heterogeneity. Eur J Hum Genet. 2004;12:668-72.

  26. Manolio TA, Brooks LD, Collins FS. A HapMap harvest of insights into the genetics of common disease. J Clin Invest. 2008;118:1590-605.

  27. Cervino AC, Tsinoremas NF, Hoffman RW. A genome-wide study of lupus: preliminary analysis and data release. Ann N Y Acad Sci. 2007; 1110:131-9.

  28. Gateva V, Sandling JK, Hom G, et al. A large-scale replication study identifies TPIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet. 2009;41:1228-33.

  29. Harley JB, Alarcón-Riquelme ME, Criswell LA, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008;40:204-10.

  30. Hom G, Graham RR, Modrek B, et al. Association of Systemic Lupus Erythematosus with C8orf13–BLK and ITGAM–ITGAX. N Engl J Med. 2008;358:900-9.

  31. Han JW, Zheng HF, Cui Y, et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythemathosus. Nat Genet. 2009;41:1234-8.

  32. Yang W, Shen N, Ye DQ, et al. Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genet. 2010;6:e1000841.

  33. Kariuki SN, Franek BS, Kumar AA, et al. Trait-stratified genome-wide association study identifies novel and diverse genetic associations with serologic and cytokine phenotypes in systemic lupus erythemathosus. Arthritis Res Ther. 2010;12:R151.

  34. Graham RR, Cotsapas C, Davies L, et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet. 2008;40:1059-61.

  35. Kozyrev SV, Abelson AK, Wojcik J, et al. Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nat Genet. 2008;40:211-6.

  36. Oishi T, Iida A, Otsubo S, et al. A functional SNP in the NKX2.5-binding site of ITPR3 promoter is associated with susceptibility to systemic lupus erythematosus in Japanese population. J Hum Genet. 2008;53:151-62.

  37. Jacob CO, Reiff A, Armstrong DL, et al. Identification of novel susceptibility genes in childhood-onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform. Arthritis Rheum. 2007;56: 4164-73.

  38. Rhodes B, Vyse TJ. The genetic of SLE: an update in the light of genomewide association studies. Rheumatology. 2008;47:1603-11.

  39. Abelson AK, Delgado-Vega AM, Kozirev SV, et al. STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk. Ann Rheum Dis. 2009;68:1746-53.

  40. Reddy MV, Velázquez-Cruz R, Baca V, et al. Genetic association of IRF5 with SLE in Mexicans: higher frequency of the risk haplotype and its homozygozity than Europeans. Hum Genet. 2007;121(6):721-7.

  41. Han S, Kim-Howard X, Deshmukh H, et al. Evaluation of imputationbased association in and around the integrin-alpha-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erhytematosus (SLE). Hum Mol Genet. 2009;18:1171-80.

  42. Baca V, Velázquez-Cruz R, Salas-Martínez G, Espinosa-Rosales F, Saldaña-Alvarez Y, Orozco L. Association analysis of the PTPN22 gene in childhood-onset systemic lupus erythematosus in Mexican population. Genes Immun. 2006;7:693-5.

  43. CH, Yao TC, Chung HT, See LC, Huo ML, Huang JL. Polymorphisms in the Promoter region of RANTES and the regulatory region of monocyte chemoattractant protein-1 among Chinese children with systemic lupus erythematosus. J Rheumatol. 2004;10:2062-7.

  44. Lee YJ, Shin KS, Kang SW, et al. Association of the oestrogen receptor alpha gene polymorphisms with disease onset in systemic lupus erythematosus. Ann Rheum Dis. 2004;10:1244-9.

  45. Von Scheven E, Elder ME. Association between beta2-glycoprotein I gene polymorphisms and pediatric SLE and antiphospholipid antibodies. Lupus. 2005;14:440-4.

  46. Armstrong DL, Reiff A, Myones BL, et al. Identification of new SLE-associated genes with a two-step Bayesian study design. Genes Immun. 2009;10:446-56.

  47. Onel KB, Hui D, Hastings D, Fryer-Biggs J, Crow MK, Onel K. Lack of association of the TP53 Arg72Pro SNP and MDR2 SNP309 with systemic erythemathosus in Caucasian, African American, and Asian children and adults. J Rheumathol. 2004;31:2062-7.

  48. Tsai YC, Yao TC, Kuo ML, Cheng TT, Huang JL. Lack of association of mannose-binding lectin gene polymorphisms with development and clinical manifestions of systemic lupus erythemathosus in Chinese children. Genes Immunol. 2009;10:487-94.

  49. Wu SA, Yeh KW, Yao TC, Huang JL. Association of herpes zoster infection with clinical characteristics and MBL2 gene polymorphisms in Chinese children with systemic lupus erythematosus. Pediatr Infect Dis J. 2011;30(8):656-60.

  50. Tsai YC, Yeh KW, Yao TC, Huang YL, Kuo ML, Huang JL. Mannosebinding lectin expression genotype in pediatric-onset systemic lupus erythematosus: association with susceptibility to renal disease and protection against infections. J Rheumatol. 2011;38(7):1429-35

  51. Granados J, Zúñiga J, Acuña-Alonso V, Rosetti F, Vargas-Alarcón G. Influencia de alelos y haplotipos del complejo principal de histocompatibilidad en la susceptibilidad a lupus generalizado en la población mexicana. Gac Med Mex. 2006;142:195-9.

  52. Jiménez-Morales S, Velázquez-Cruz R, Ramírez-Bello J, et al. Tumor necrosis factor-alpha is a common genetic risk factor for asthma, juvenile rheumatoid arthritis and systemic lupus erythemathosus in a mexican pediatric population. Hum Immunol. 2009;70:251-6.

  53. Lee YI, Harley JB, Nath SK. Meta-analysis of TNF- promoter -308A/G polymorphism ans SLE susceptibility. Eur J Hum Genet. 2006;14:364-71.

  54. Kroeger KM, Carville KS, Abraham LJ. The -308 tumor necrosis factor-a promoter polymorphism effects transcription. Mol Immunol. 1997;34:391-9.

  55. Baseggio L, Bartholin L, Chantome A, Charlot C, Rimokh R, Salles G. Allele-specific binding to the -308 single nucleotide polymorphisms site in the tumour necrosis factor-alpha promoter. Eur J Immunogenet. 2004;31;15-9.

  56. Sigurdsson S, Nordmark G, Goring HH, et al. Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J Hum Genet. 2005;76:528-37.

  57. Kyogoku C, Tsuchiya N. A compass that points to lupus: genetic studies on type I interferon pathway. Genes Immun. 2007;8:445-55.

  58. Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008; 224:166-82.

  59. Prokunina L, Castillejo-López C, Oberg F, et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet. 2002;32:666-9.

  60. Velázquez-Cruz R, Orozco L, Espinosa-Rosales F, et al. Association of PDCD1 polymorphisms with childhood-onset systemic lupus erythematosus. Eur J Hum Genet. 2007;15:336-41.

  61. Vang T, Congia M, Macis MD, et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet. 2005;37:1317-9.

  62. Lee YH, Rho YH, Choi SJ, et al. The PTPN22 C1858T functional polymorphism and autoimmune diseases--a meta-analysis. Rheumatology. 2007;46(1):49-56.

  63. Nath SK, Han S, Kim-Howard X, et al. A nonsynonymous functional variant in integrin-alpha (M) (encoded by ITGAM) is associated with systemic lupus erhytematosus. Nat Genet. 2008;40:152-4.

  64. Buyon JP, Shadick N, Berkman R, et al. Surface expression of Gp 165/95, the complement receptor CR3, as a marker of disease activity in systemic lupus erythematosus. Clin Immunol Immunopathol. 1998;46:141-9.

  65. Sachs UJ, Chavakis T, Fung L, et al. Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion. Blood. 2004;104:727-34.

  66. Savarese E, Chae OW, Trowitzsch S, et al. U1 small nuclear ribonucleoprotein immune complex induce type 1 interferon in plasmacytoid dendritic cells through TLR7. Blood. 2006;107:3229-34.

  67. García Ortiz H, Velázquez Cruz R, Espinosa Rosales F, Jiménez Morales S, Baca V, Orozco L. Association of TLR7 copy number variation with susceptibility to childhood-onset systemic lupus erhytematosus in Mexican population. Ann Rheum Dis. 2010;69:1861-5.

  68. Osburn WO, Kensler TW. Nrf2 signaling: an adaptative response pathway for protection against environmental toxic insults. Mutat Res. 2008;659:31-9.

  69. Lau A, Villeneuve NF, Sun Z, Wong PK, Zhang DD. Dual roles of Nrf2 in cancer. Pharmacol Res. 2008;58:262-70.

  70. Suh JH, Shenvi SV, Dixon BM, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, wich is reversible with lipoic acid. Proc Natl Acad Sci USA. 2004;101:3381-6.

  71. Fukushima-Uesaka H, Saito Y, Maekawa K, et al. Genetic variations and haplotype structures of transcriptional factor Nrf2 and its cytosolic reservoir protein Keap1 in Japanese. Drug Metab Pharmacokinet. 2007;22:212-9.

  72. Marzec JM, Christie JD, Reddy SP, et al. Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. FASEB J. 2007;21:2237-46.

  73. Arisawa T, Tahara T, Shibata T, et al. The relationship between helicobacter pylori infection and promoter polymorphism of the Nrf2 gene in chronic gastritis. Int J Mol Med. 2007;19:143-8.

  74. Córdova EJ, Velázquez-Cruz R, Centeno F, Baca V, Orozco L. The NRF2 gene variant, -653G/A, is associated with nephritis in childhood-onset systemic lupus erhytematosus. Lupus. 2010;19:1237-42.

  75. Lima G, Soto-Vega E, Atisha-Fregoso Y, et al. MCP-1, RANTES, and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus. Hum Immunol. 2007;68:980-5.

  76. Doniz-Padilla L, Martínes-Jiménez V, Niño-Moreno P, et al. Expression and function of Cbl-b in T cells from patients with systemic lupus erythematosus, and detection of the 2126A/G Cblb gene polymorphism in the Mexican mestizo population. Lupus. 2011;20:628-35




2020     |     www.medigraphic.com