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Genetic influences on rheumatoid arthritis in african americans

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Abstract

Rheumatoid arthritis is a common autoimmune disease characterized by inflammation of the synovial membrane of diarthrodial joints, which often leads to joint damage and disability. There are known associations between major histocompatibility complex class II alleles and susceptibility to rheumatoid arthritis and its severity in Caucasians. African Americans, an admixed population in the United States, has been underrepresented in genetic studies of the susceptibility and severity of rheumatoid arthritis. With the advent of biologic agents, which target specific molecules of the immune system (e.g., tumor necrosis factor, interleukin-1), biologic markers of treatment response in Caucasians and in African Americans would be clinically useful.

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References

  1. Zhang Z, Bridges SL, Jr. Pathogenesis of rheumatoid arthritis: role of B lymphocytes. Rheum Dis Clin North Am 2001;27:335–353.

    Article  PubMed  CAS  Google Scholar 

  2. Pincus T, Brooks RH, Callahan LF: Prediction of long-term mortality in patients with rheumatoid arthritis according to simple questionaire and joint count measures. Ann Intern Med 1994;120(1): 26–34.

    PubMed  CAS  Google Scholar 

  3. Seldin MF, Amos CI, Ward R, Gregersen PK: The genetics revolution and the assault on rheumatoid arthritis. Arthritis Rheum 1999;42(6):1071–1079.

    Article  PubMed  CAS  Google Scholar 

  4. Goodman AH: Why genes don't count (for racial differences in health). Am J Public Health 2000;90(11):1699–1702.

    PubMed  CAS  Google Scholar 

  5. Halushka MK, Fan JB, Bentley K, et al: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet 1999;22(3):239–247

    Article  PubMed  CAS  Google Scholar 

  6. Schwartz RS: Racial profiling in medical research. N Engl J Med 2001;344(18):1392–1393.

    Article  PubMed  CAS  Google Scholar 

  7. Parra EJ, Marcini A, Akey, et al: Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet 1998;63(6): 1839–1851.

    Article  PubMed  CAS  Google Scholar 

  8. Reitnauer PJ, Go RC, Acton RT, et al: Evidence for genetic admixture as a determinant in the occurrence of insulin-dependent diabetes mellitus in U.S. blacks. Diabetes 1982;31(6 Pt 1):532–537.

    Article  PubMed  CAS  Google Scholar 

  9. Glass B, Li CC: The dynamics of racial intermixture—an analysis based on the American Negro. Am J Hum Genet 1953;5:1–19.

    PubMed  CAS  Google Scholar 

  10. Acton RT, Harman L, Go RC, Tseng ML, Bias W: Comparison of HLA phenotypes among African Americans from Alabama, Maryland, and North Carolina. Transplant Proc 1993;25(4):2404–2407.

    PubMed  CAS  Google Scholar 

  11. Mori M, Beatty PG, Graves M, Boucher KM, Milford EL: HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry. Transplantation 1997;64(7):1017–1027.

    Article  PubMed  CAS  Google Scholar 

  12. Vyse TJ, Todd JA: Genetic analysis of autoimmune disease. Cell 1996;85(3):311–318.

    Article  PubMed  CAS  Google Scholar 

  13. Stastmy P: Association of the B cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med 1978;298:869–871.

    Google Scholar 

  14. Ollier W, Thomson W: Population genetics of rheumatoid arthritis. Rheum Dis Clin North Am 1992;18(4):741–759.

    PubMed  CAS  Google Scholar 

  15. Gregersen PK, Silver J, Winchester R The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987;30: 1205–1213.

    Article  PubMed  CAS  Google Scholar 

  16. Rigby AS, Silman AJ, Voelm L, et al: Investigating the HLA component in rheumatoid arthritis: an additive (dominant) mode of inheritance is rejected, a recessive mode is preferred. Genet Epidemiol 1991;8(3):153–175.

    Article  PubMed  CAS  Google Scholar 

  17. Rigby AS, Voelm L, Silman AJ: Epistatic modeling in rheumatoid arthritis: an application of the Risch theory. Genet Epidemiol 1993;10(5):311–320.

    Article  PubMed  CAS  Google Scholar 

  18. Ollier W, Thomson W: Population genetics of rheumatoid arthritis. Rheum Dis Clin North Am 1992; 18(4):741–759.

    PubMed  CAS  Google Scholar 

  19. McDaniel DO, Alarcón GS, Pratt PW, Reveille JD: Most African-American patients with rheumatoid arthritis do not have the rheumatoid antigenic determinant (epitope). Ann Intern Med 1995; 123:181–187.

    PubMed  CAS  Google Scholar 

  20. Teller K, Budhai L, Zhang M, Haramati N, Keiser HD, Davidson A: HLA-DRB: 1 and DQB typing of Hispanic American patients with rheumatoid arthritis: the “shared epitope” hypothesis may not apply. J Rheumatol 1996;23(8): 1363–1368.

    PubMed  CAS  Google Scholar 

  21. Nichol FE, Woodrow JC: HLADR antigens in Indian patients with rheumatoid arthritis [letter]. Lancet 1981;1(8213):220–221.

    Article  PubMed  CAS  Google Scholar 

  22. Sanchez B, Moreno I, Magarino R, et al: HLA-DR w 10 confers the highest susceptibility to rheumatoid arthritis in a Spanish population. Tissue Antigens 1990;36(4): 174–176.

    PubMed  CAS  Google Scholar 

  23. Gao X, Gazit E, Livneh A, Stastny P: Rheumatoid arthritis in Israeli Jews: shared sequences in the third hypervariable region of DRB1 alleles are associated with susceptibility. J Rheumatol 1991;18(6): 801–803.

    PubMed  CAS  Google Scholar 

  24. Hasstedt SJ, Clegg DO, Ingles L, Ward RH: HLA-1 inked rheumatoid arthritis. Am J Hum Genet 1994;55(4):738–746.

    PubMed  CAS  Google Scholar 

  25. Corrélis F, Faure S, Maritinez M, et al: New susceptibility locus for rheumatoid arthritis suggested by agenome-wide linkage study. Proc Natl Acad Sci USA 1998;95(18): 10,746–10,750.

    Google Scholar 

  26. Barton A, Eyre S, Myerscough A, et al: High resolution linkage and association mapping identifies a novel rheumatoid arthritis susceptibility locus homologous to one linked to two rat models of inflammatory arthritis. Hum Mol Genet 2001;10(18):1901–1906.

    Article  PubMed  CAS  Google Scholar 

  27. Jawaheer D, Seldin MF, Amos CI, et al: A genome-wide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases. Am J Human Genet 2001;68: 927–936.

    Article  CAS  Google Scholar 

  28. Fishman D, Faulds G, Jeffery R, et al: The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 1998;102(7):1369–1376.

    PubMed  CAS  Google Scholar 

  29. Osiri M, Whitworth W, McNicholl J, Jonas B, Moreland LW, Bridges SL, Jr. A novel single nucleotide polymorphism and five haplotypes in the 5′ flanking region of the IL-6 gene: differences between Caucasians and African-Americans: Arthritis Rheum 1999; 42(Suppl):S196 (abstract).

    Google Scholar 

  30. Chu CQ, Field M, Feldmann M, Maini RN: Loca lization of tumor necrosis factor alpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis. Arthritis Rheum 1991;34(9):1125–1132.

    Article  PubMed  CAS  Google Scholar 

  31. Brennan FM, Maini RN, Feldmann M: Role of pro-inflammatory cytokines in rheumatoid arthritis. Springer Semin Immunopathol 1998;20(1–2):133–147.

    Article  PubMed  CAS  Google Scholar 

  32. Wilson AG, de Vries N, van de Putte LB, Duff GW: A tumour necrosis factor alpha polymorphism is not associated with rheumatoid arthritis. Ann Rheum Dis 1995;54(7):601–603.

    PubMed  CAS  Google Scholar 

  33. Campbell DA, Nelson S, Madhok R, Field M, Gallagher G: TNF Nco-1 RFLP is not an independent risk factor in rheumatoid arthritis. Eur J Immunogenet 1994;21(6): 461–467.

    Article  PubMed  CAS  Google Scholar 

  34. Field M, Gallagher G, Eskdale J, et al: Tumor necrosis factor locus polymorphisms in rheumatoid arthritis. Tissue Antigens 1997; 50(3):303–307.

    PubMed  CAS  Google Scholar 

  35. Vinasco J, Beraun Y, Nieto A, et al: Polymorphism at the TNF loci in rheumatoid arthritis. Tissue Antigens 1997;49(1):74–78.

    PubMed  CAS  Google Scholar 

  36. Mulcahy B, Waldron-Lynch F, McDennott MF, et al: Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis. Am J Hum Genet 1996;59(3):676–683.

    PubMed  CAS  Google Scholar 

  37. Hajeer AH, Worthington J, Silman AJ, Ollier WE: Association of tumor necrosis factor microsatellite polymorphisms with HLA-DRB1 *04-bearing haplotypes in rheumatoid arthritis patients. Arthritis Rheum 1996;39(7): 1109–1114.

    Article  PubMed  CAS  Google Scholar 

  38. Mu H, Chen JJ, Jiang Y, King M-C, Thomson G, Criswell LA: Tumor necrosis factor a microsatellite polymorphism is associated with rheumatoid arthritis severity through an interaction with the HLA-DRB1 share depitope. Arthritis Rheum 1999;42(3):438–442.

    Article  PubMed  CAS  Google Scholar 

  39. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW: Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transriptional activation. Proc Natl Acad Sci USA 1997;94(7):3195–3199.

    Article  PubMed  CAS  Google Scholar 

  40. Paulus HE, van der Heijde DM, Bulpitt KJ, Gold RH: Monitoring radio graphic changes in early rheumatoid arthritis. J Rheumatol 1996;23(5):801–805.

    PubMed  CAS  Google Scholar 

  41. van der Heijde DM, van Leeuwen MA, van Riel PL, van de Putte LB: Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp's method (van der Heijde modification). J Rheumatol 1995; 22(9):1792–1796.

    PubMed  Google Scholar 

  42. Corbett M, Dalton S, Young A, Silman A, Shipley M: Factors predecting death, survival and functional outcome in a prospective study of early rheumatoid disease over fifteen years. Br J Rheumatol 1993;32(8):717–723.

    Article  PubMed  CAS  Google Scholar 

  43. Nepom GT, Byers P, Seyfried C, et al: HLA genes associated with rheumatoid arthritis: identification of susceptibility alleles using specificoligonucleotide probes. Arthritis Rheum 1989;32(1):15–21.

    Article  PubMed  CAS  Google Scholar 

  44. Weyand CM, McCarthy TG, Goronzy JJ: Correlation between disease phenotype and genetic heterogeneity in rheumatoid arthritis. J Clin Invest 1995;95:2120–2126.

    Article  PubMed  CAS  Google Scholar 

  45. Weyand CM, Xie C, Goronzy JJ: Homozygosity for the HLA-DRB1 allele selects for extraarticular manifestations in rheumatoid arthritis. J Clin Invest 1992;89(6): 2033–2039.

    PubMed  CAS  Google Scholar 

  46. Ueno Y, Iwaki Y, Terasaki PI, et al: HLA-DR4 in Negro and Mexican rheumatoid arthritis patients. J Rheumatol 1981;8(5):804–807.

    PubMed  CAS  Google Scholar 

  47. Jawaheer D, Thomson W, Mac-Gregor AJ, et al: “Homozygosity” for the HLA-DR shared epitope contributes the highest risk for rheumatoid arthritis concordance in identical twins. Arthritis Rheum 1994;37(5):681–686.

    Article  PubMed  CAS  Google Scholar 

  48. Mody GM, Meyers OL: Rheumatoid arthritis in blacks in South Africa. Ann Rheum Dis 1989; 48(1):69–72.

    PubMed  CAS  Google Scholar 

  49. Jordan JM: Effect of race and ethnicity on outcomes in arthritis and rheumatic conditions. Curr Opin Rheumatol 1999;11(2):98–103.

    Article  PubMed  CAS  Google Scholar 

  50. Karr RW, Rodey GE, Lee T, Schwartz BD: Association of HLA-DRw4 with rheumatoid arthritis in black and white patients. Arthritis Rheum 1980;23(11): 1241–1245.

    Article  PubMed  CAS  Google Scholar 

  51. Goel N, Ortel TL, Bali D, et al: Familial antiphospholipid antibody syndrome: criteria for disease and evidence for autosomal dominant inheritance. Arthritis Rheum 1999;42(2):318–327.

    Article  PubMed  CAS  Google Scholar 

  52. Alarif LI, Ruppert GB, Wilson R Jr, Barth WF: HLA-DR antigens in Blacks with rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol 1983;10(2): 297–300.

    PubMed  CAS  Google Scholar 

  53. Alarcón GS, Koopman WJ, Acton RT, Barger BO: DR antigen distribution in Blacks with rheumatoid arthritis. J Rheumatol 1983;10(4): 579–583.

    PubMed  Google Scholar 

  54. Alarcón GS, Barger BO, Acton RT, Koopman WJ. HLA antigens and gold toxicity in American blacks with rheumatoid arthritis. Rheumatol Int 1986;6(1):13–17.

    Article  PubMed  Google Scholar 

  55. Adebajo A, Davis P: Rheumatic diseases in A frican blacks. Semin Arthritis Rheum 1994;24(2): 139–153.

    Article  PubMed  CAS  Google Scholar 

  56. Mitchell JM, Burkhauser RV, Pincus T: The importance of age, education, and comorbidity in the substantial earnings losses of individuals with symmetric polyarthritis. Arthritis Rheum 1988; 31(3):348–357.

    Article  PubMed  CAS  Google Scholar 

  57. Callahan LF, Pincus T, Huston JW III, Brooks RH, Nance EP Jr, Kaye JJ: Measures of activity and damage in rheumatoid arthritis: depiction of changes and prediction of mortality over five years. Arthritis Care Res 1997;10(6):381–394.

    Article  PubMed  CAS  Google Scholar 

  58. Sang KG, Cerhan JR, Kolluri S, Ohashi K, Hunninghake GW, Schwartz DA: Cigarette smoking and rheumatoid arthritis severity. Ann Rheum Dis 1997;56(8): 463–469.

    Google Scholar 

  59. MacGregor A, Olliver W, Thomson W, Jawaheer D, Silman A: HLA-DRB1 *0401/0404 genotype and rheumatoid arthritis: increased association in men, young age at onset, and disease severity. J Rheumatol 1995;22(6):1032–1036.

    PubMed  CAS  Google Scholar 

  60. Plant MJ, Jones PW, Saklatvala J, Olliev WE, Dawes PT: Patterns of radiological progression in early rheumatoid arthritis: results of an 8 year prospective study. J Rheumatol 1998;25(3):417–426.

    PubMed  CAS  Google Scholar 

  61. Weyand CM, Hicok KC, Conn DL, Goronzy JJ: The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. Ann Intern Med 1992;117:801–806.

    PubMed  CAS  Google Scholar 

  62. Brinkman BM, Huizinga TW, Kurban SS, et al. Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis: association with susceptihility to, or severity of disease? Br J Rheumatol 1997; 36(5):516–521.

    Article  PubMed  CAS  Google Scholar 

  63. Kaijzel EL, van Krugten MV, Brinkman BM, et al: Functional analysis of a human tumor necrosis factor alpha (TNF-alpha) promoter polymorphism related to joint damage in rheumatoid arthritis. Mol Med 1998;4(11):724–733.

    PubMed  CAS  Google Scholar 

  64. Kleyn PW, Vesell ES: Genetic variation as a guide to drug development. Science 1998;281: 1820–1821.

    Article  PubMed  CAS  Google Scholar 

  65. Black AJ, McLeod HL, Capell HA, et al: Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathoprine. Ann Intern Med 1998;129:716–718.

    PubMed  CAS  Google Scholar 

  66. Arranz MJ, Collier DA, Munro J et al: Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine. Neurosci Lett 1996;217 (2–3): 177–178.

    Article  PubMed  CAS  Google Scholar 

  67. Poirier J, Davignon J, Bouthillier D, Kogan S, Bertrand P, Gauthier S: Apolipoprotein E polymorphism and Alzheimer's disease. Lancet 1993;342(8873):697–699.

    Article  PubMed  CAS  Google Scholar 

  68. O'Dell JR, Nepom BS, Haire C, et al: HLA-DRB 1 typing in rheumatoid arthritis: predicting response to specific treatments. Ann Rheum Dis 1998;57(4):209–213.

    Article  PubMed  Google Scholar 

  69. Moreland LW, Baungartner SW, Schiff MH, et al: Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997; 337(3):141–147.

    Article  PubMed  CAS  Google Scholar 

  70. Moreland LW, Schiff MH, Baumgartner SW, et al: Etane recept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med 1999;130(6):478–486.

    PubMed  CAS  Google Scholar 

  71. Elliott MJ, Maini RN, Feldmann M, et al: Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994;344(8930):1105–1110.

    Article  PubMed  CAS  Google Scholar 

  72. Lipsky PE, van der Heijde DM, St Clair EW, et al Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 2000;343(22):1594–1602.

    Article  PubMed  CAS  Google Scholar 

  73. Kimberly RP, Moreland LW, Wu J, Edberg JC, Weinblatt ME, Blosch C: Occurrence of infection varies with Fc receptor genotype. Arthritis Rheum 1998;41(9) (Suppl): S273 (abstract).

    Google Scholar 

  74. Kimberly RP, Moreland LW, Gibson A, Weinblatt M, Bosch C: Susceptibility to infection may vary with TNF promoter genotype. Arthritis Rheum 1998;41(9) (Suppl): S273 (abstract).

    Google Scholar 

  75. Bresnihan B: The safety and efficacy of interleukin-1 receptorantagonist in the treatment of rheumatoid arthritis. Semin Arthritis Rheum 2001;30(5) (Suppl 2):17–20.

    Article  PubMed  CAS  Google Scholar 

  76. Loetscher H, Pan YC, Lahm HW, et al: Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell 1990;61(2):351–359.

    Article  PubMed  CAS  Google Scholar 

  77. Schall TJ, Lewis M, Koller KJ, et al: Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell 1990; 61(2):361–370.

    Article  PubMed  CAS  Google Scholar 

  78. Fuchs P, Strehl S, Dworzak M, Himmler A, Ambros PF: Structure of the human TNF receptor 1 (p60) gene (TNFR 1) and localization to chromosome 12pl 3. Genomics 1992;13(1):219–224.

    Article  PubMed  CAS  Google Scholar 

  79. Santee SM, Owen-Schaub LB: Human tumor necrosis factor receptor p75/80 (CD 120b) gene structure and promoter characterization. J Biol Chem 1996;271 (35): 21,151–21,159.

    CAS  Google Scholar 

  80. Drysdale CM, McGraw DW, Stack CB, et al: Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA 2000;97(19): 10,483–10,488.

    Article  CAS  Google Scholar 

  81. Schiff MH: Leflunomide versus methotrexate: a comparison of the European and American experience. Scand J Rheumat Suppl 1999;112:31–35.

    Article  CAS  Google Scholar 

  82. Sandoval DM, Alarcón GS, Morgan SL: Adverse events in methotrexate-treated rheumatoid arthritis patients. Br J Rheumatol 1995;(34 Suppl 2):49–56.

    PubMed  Google Scholar 

  83. Bathon JM, Martin RW, Fleischmann RM, et al: A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343: 1586–1593.

    Article  PubMed  CAS  Google Scholar 

  84. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001;344(22):1659–1667.

  85. Exner DV, Dries DL, Domanski MJ, Cohn JN: Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med 2001;344(18): 1351–1357.

    Article  PubMed  CAS  Google Scholar 

  86. Reddy KR, Hoofnagle JH, Tong MJ, et al: Racial differences in responses to therapy with interferon in chronic hepatitis C. Consensus Interferon Study Group. Hepatology 1999;30(3): 787–793.

    Article  PubMed  CAS  Google Scholar 

  87. Kinzie JL, Naylor PH, Nathani MG, et al: African Americans with genotype 1 treated with interferon forchronic hepatitis C have a lower end of treatment response than Caucasians. J Viral Hepat 2001; 8(4):264–269.

    Article  PubMed  CAS  Google Scholar 

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  1. Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 35294-0007, Birmingham, AL

    Laura B. Hughes, Larry W. Moreland & S. Louis Bridges Jr. MD, PhD

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  1. Laura B. Hughes
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  2. Larry W. Moreland
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  3. S. Louis Bridges Jr. MD, PhD
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Correspondence to S. Louis Bridges Jr. MD, PhD.

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Hughes, L.B., Moreland, L.W. & Bridges, S.L. Genetic influences on rheumatoid arthritis in african americans. Immunol Res 26, 15–26 (2002). https://doi.org/10.1385/IR:26:1-3:015

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