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.