Generic placeholder image

Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Genetic Alleles Associated with SLE Susceptibility and Clinical Manifestations in Hispanic Patients from the Dominican Republic

Author(s): Zheng Liu, Yangsheng Yu, Yinshi Yue, Michelene Hearth-Holmes, Persio David Lopez, Carmen Tineo, Glenny Paulino, Wei-Neng Fu*, Esthela Loyo* and Kaihong Su*

Volume 19, Issue 3, 2019

Page: [164 - 171] Pages: 8

DOI: 10.2174/1566524019666190424130809

Price: $65


Purpose: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with marked disparities in prevalence and disease severity among different ethnic groups. The purpose of this study is to characterize a Latin American cohort and identify genetic risk factors for developing SLE and its end-organ manifestations in this Latin Hispanic cohort.

Methods: A total of 201 SLE cases and 205 non-diseased controls were recruited in the Dominican Republic (DR). Cases were defined according to the 1997 revised American College of Rheumatology criteria for the classification of SLE. Genomic DNA was prepared from whole blood and applied to genotyping analyses for 42 single nucleotide polymorphisms (SNPs) that have been implicated in autoimmune diseases, including SLE, in other ethnic populations. Data were analyzed by Fisher’s Exact Probability Test.

Results: In this cohort, SNP rs9271366 (tag SNP for HLA-DRB1*15:01) confers the highest risk for SLE among the 13 MHC gene alleles that display association with SLE (p = 8.748E-10; OR = 3.5). Among the 26 non-MHC gene alleles analyzed, SNP rs2476601 in PTPN22 gene confers the highest risk for SLE (p = 0.0001; OR = 5.6). ITGAM, TNFSF4, TNIP1, STAT4, CARD11, BLK, and TNXB gene alleles were confirmed as SLE-susceptible alleles in the DR cohort. However, IRF5 and TNFAIP3 gene alleles, established risk factors for SLE in populations of European and Asian ancestry, are not significantly associated with SLE in this cohort. We also defined a novel HLA-DRA haplotype that confers an increased risk for lupus nephritis (LN) and alleles in HLA-DRA2 and TNFSF4 genes as genetic risk factors for developing neuropsychiatric (NP) SLE.

Conclusion: Our data suggest that the Latin American population shares some common genetic risk factors for SLE as other populations, but also has distinct risk gene alleles that contribute to SLE susceptibility and development of LN and NPSLE. This is the first study focusing on genetic risk factors for SLE in the DR, a Latin American population that has never been characterized before.

Keywords: Genetic alleles lupus, systemic lupus erythematosus, SLE, genetic alleles, hispanic patients, genetic risk factors, autoimmune disease.

Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med 2008; 358(9): 929-39.
Tsokos GC. Systemic lupus erythematosus. N Engl J Med 2011; 365(22): 2110-21.
Fernandez M, Alarcon GS, Calvo-Alen J, et al. A multiethnic, multicenter cohort of patients with systemic lupus erythematosus (SLE) as a model for the study of ethnic disparities in SLE. Arthritis Rheum 2007; 57(4): 576-84.
Uribe AG, McGwin G, Jr Reveille JD, Alarcon GS. What have we learned from a 10-year experience with the LUMINA (Lupus in Minorities; Nature vs. nurture) cohort? Where are we heading? Autoimmun Rev 2004; 3(4): 321-9.
Petri M, Perez-Gutthann S, Longenecker JC, Hochberg M. Morbidity of systemic lupus erythematosus: Role of race and socioeconomic status. Am J Med 1991; 91(4): 345-53.
Reveille JD, Moulds JM, Ahn C, et al. Systemic lupus erythematosus in three ethnic groups: I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset. LUMINA Study Group. Lupus in minority populations, nature versus nurture. Arthritis Rheum 1998; 41(7): 1161-72.
Ceccarelli F, Perricone C, Borgiani P, et al. Genetic factors in systemic lupus erythematosus: Contribution to disease phenotype. J Immunol Res 2015; 2015745647
Goulielmos GN, Zervou MI, Vazgiourakis VM, Ghodke-Puranik Y, Garyfallos A, Niewold TB. The genetics and molecular pathogenesis of systemic lupus erythematosus (SLE) in populations of different ancestry. Gene 2018; 668: 59-72.
James JA. Clinical perspectives on lupus genetics: Advances and opportunities. Rheum Dis Clin North Am 2014; 40(3): 413-32. vii.
Rosetti F, de la Cruz A, Crispin JC. Gene-function studies in systemic lupus erythematosus. Curr Opin Rheumatol 2019; 31(2): 185-92.
Teruel M, Alarcon-Riquelme ME. The genetic basis of systemic lupus erythematosus: What are the risk factors and what have we learned. J Autoimmun 2016; 74: 161-75.
Teruel M, Alarcon-Riquelme ME. Genetics of systemic lupus erythematosus and sjogren’s syndrome: An update. Curr Opin Rheumatol 2016; 28(5): 506-14.
Yuan YJ, Luo XB, Shen N. Current advances in lupus genetic and genomic studies in Asia. Lupus 2010; 19(12): 1374-83.
Pons-Estel GJ, Catoggio LJ, Cardiel MH, et al. Lupus in latin-american patients: Lessons from the GLADEL cohort. Lupus 2015; 24(6): 536-45.
Lu R, Robertson JM, Bruner BF, et al. Multiple autoantibodies display association with lymphopenia, proteinuria, and cellular casts in a large, ethnically diverse SLE patient cohort. Autoimmune Dis 2012; 2012819634
Morris DL, Taylor KE, Fernando MM, et al. Unraveling multiple MHC gene associations with systemic lupus erythematosus: Model choice indicates a role for HLA alleles and non-HLA genes in europeans. Am J Hum Genet 2012; 91(5): 778-93.
Fernando MM, Stevens CR, Sabeti PC, et al. Identification of two independent risk factors for lupus within the MHC in united kingdom families. PLoS Genet 2007; 3(11)e192
Kitajima H, Sonoda M, Yamamoto K. HLA and SNP haplotype mapping in the japanese population. Genes Immun 2012; 13(7): 543-8.
Namjou B, Kim-Howard X, Sun C, et al. PTPN22 association in systemic lupus erythematosus (SLE) with respect to individual ancestry and clinical sub-phenotypes. PLoS One 2013; 8(8)e69404
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(9): 900-9.
Kawasaki A, Ito I, Hikami K, et al. Role of STAT4 polymorphisms in systemic lupus erythematosus in a japanese population: A case-control association study of the STAT1-STAT4 region. Arthritis Res Ther 2008; 10(5): R113.
Gateva V, Sandling JK, Hom G, et al. A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009; 41(11): 1228-33.
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 erythematosus. Nat Genet 2009; 41(11): 1234-7.
Adrianto I, Wang S, Wiley GB, et al. Association of two independent functional risk haplotypes in TNIP1 with systemic lupus erythematosus. Arthritis Rheum 2012; 64(11): 3695-705.
Julia A, Lopez-Longo FJ, Venegas PJJ, et al. Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus. Arthritis Res Ther 2018; 20(1): 100.
Ramos PS, Brown EE, Kimberly RP, Langefeld CD. Genetic factors predisposing to systemic lupus erythematosus and lupus nephritis. Semin Nephrol 2010; 30(2): 164-76.
Wunnenburger S, Schultheiss UT, Walz G, et al. Associations between genetic risk variants for kidney diseases and kidney disease etiology. Sci Rep 2017; 7(1): 13944.
Xu R, Li Q, Liu R, et al. Association analysis of the MHC in lupus nephritis. J Am Soc Nephrol 2017; 28(11): 3383-94.
Ruiz-Narvaez EA, Fraser PA, Palmer JR, et al. MHC region and risk of systemic lupus erythematosus in african american women. Hum Genet 2011; 130(6): 807-15.
Barcellos LF, May SL, Ramsay PP, et al. High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions. PLoS Genet 2009; 5(10)e1000696
Pons-Estel BA, Catoggio LJ, Cardiel MH, et al. The GLADEL multinational latin american prospective inception cohort of 1,214 patients with systemic lupus erythematosus: Ethnic and disease heterogeneity among “Hispanics”. Medicine (Baltimore) 2004; 83(1): 1-17.

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy