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1.  The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus 
Genes and Immunity  2011;12(8):667-671.
The major histocompatibility complex (MHC) class II transactivator gene (CIITA) encodes an important transcription factor required for HLA class II MHC-restricted antigen presentation. MHC genes, including the HLA class II DRB1*03:01 allele, are strongly associated with systemic lupus erythematosus (SLE). Recently the rs4774 CIITA missense variant (+1632G/C) was reported to be associated with susceptibility to multiple sclerosis. In the current study, we investigated CIITA, DRB1*03:01 and risk of SLE using a multi-stage analysis. In stage 1, 9 CIITA variants were tested in 658 cases and 1,363 controls (N = 2,021). In stage 2, rs4774 was tested in 684 cases and 2,938 controls (N = 3,622). We also performed a meta-analysis of the pooled 1,342 cases and 4,301 controls (N = 5,643). In stage 1, rs4774*C was associated with SLE (odds ratio [OR] = 1.24, 95% confidence interval [95% CI] = 1.07–1.44, P = 4.2 × 10−3). Similar results were observed in stage 2 (OR = 1.16, 95% CI = 1.02–1.33, P = 8.5×10−3) and the meta-analysis of the combined dataset (OR = 1.20, 95% CI = 1.09–1.33, Pmeta = 2.5×10−4). In all three analyses, the strongest evidence for association between rs4774*C and SLE was present in individuals who carried at least one copy of DRB1*03:01 (Pmeta= 1.9×10−3). Results support a role for CIITA in SLE, which appears to be stronger in the presence of DRB1*03:01.
PMCID: PMC3387803  PMID: 21614020
systemic lupus erythematosus; autoimmunity; major histocompatibility complex; HLA; CIITA; MHC2TA
2.  Role of MYH9 and APOL1 in African and non-African populations with Lupus Nephritis 
Genes and Immunity  2011;13(3):232-238.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected p-value of p < 2.03 × 10−3 were observed between LN and MYH9 in EAs (N=4620), with the most pronounced association at rs2157257 (p = 4.7 × 10−4; odds ratio [OR]=1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, p = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population and presents novel insight into the potential role of MYH9 in LN in EAs.
PMCID: PMC3330160  PMID: 22189356
MYH9; APOL1; lupus nephritis; systemic lupus erythematosus; multiethnic association study
3.  Peripheral blood gene expression profiling in Sjögren’s syndrome 
Genes and Immunity  2009;10(4):285-296.
Sjögren’s syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. Affected cases commonly present with oral and ocular dryness, thought to be the result of inflammatory cell-mediated gland dysfunction. To identify important molecular pathways involved in SS, we used high-density microarrays to define global gene expression profiles in peripheral blood. We first analyzed 21 SS cases and 23 controls and identified a prominent pattern of overexpressed genes that are inducible by interferons (IFNs). These results were confirmed by evaluation of a second independent dataset of 17 SS cases and 22 controls. Additional inflammatory and immune-related pathways with altered expression patterns in SS cases included B and T cell receptor, IGF-1, GM-CSF, PPARα/RXRα, and PI3/AKT signaling. Exploration of these data for relationships to clinical features of disease revealed that expression levels for most IFN-inducible genes were positively correlated with titers of anti-Ro/SSA (P<0.001) and anti-La/SSB (P<0.001) autoantibodies. Diagnostic and therapeutic approaches targeting IFN signaling pathway may prove most effective in the subset of SS cases who produce anti-Ro/SSA and anti-La/SSB autoantibodies. Our results strongly support innate and adaptive immune processes in the pathogenesis of SS and provide numerous candidate disease markers for further study.
PMCID: PMC3273959  PMID: 19404300

Results 1-3 (3)