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1.  Meta-analysis and Imputation Identifies a 109 kb Risk Haplotype Spanning TNFAIP3 Associated with Lupus Nephritis and Hematologic Manifestations 
Genes and immunity  2009;10(5):470-477.
TNFAIP3 encodes the ubiquitin modifying enzyme, A20, a key regulator of inflammatory signaling pathways. We previously reported association between TNFAIP3 variants and systemic lupus erythematosus (SLE). In order to further localize the risk variant(s), we performed a meta-analysis using genetic data available from two Caucasian case/control datasets (1453 total cases, 3381 total controls) and 713 SLE trio families. The best result was found at rs5029939 (P = 1.67 × 10−14, OR = 2.09, 95% CI 1.68–2.60). We then imputed SNPs from the CEU Phase II HapMap using genotypes from 431 SLE cases and 2155 controls. Imputation identified eleven SNPs in addition to three observed SNPs, which together, defined a 109 kb SLE risk segment surrounding TNFAIP3. When evaluating whether the rs5029939 risk allele was associated with SLE clinical manifestations, we observed that heterozygous carriers of the TNFAIP3 risk allele at rs5029939 have a two-fold increased risk of developing renal or hematologic manifestations compared to homozygous non-risk subjects. In summary, our study strengthens the genetic evidence that variants in the region of TNFAIP3 influence risk for SLE, particularly in patients with renal and hematologic manifestations, and narrows the risk effect to a 109 kb DNA segment that spans the TNFAIP3 gene.
doi:10.1038/gene.2009.31
PMCID: PMC2714405  PMID: 19387456
systemic lupus erythematosus; TNFAIP3; imputation; meta-analysis
2.  Identification of a transcription factor IIIA-interacting protein 
Nucleic Acids Research  2000;28(9):1986-1993.
Transcription factor IIIA (TFIIIA) activates 5S ribosomal RNA gene transcription in eukaryotes. The protein from vertebrates has nine contiguous Cys2His2 zinc fingers which function in nucleic acid binding, and a C-terminal region involved in transcription activation. In order to identify protein partners for TFIIIA, yeast two-hybrid screens were performed using the C-terminal region of Xenopus TFIIIA as an attractor and a rat cDNA library as a source of potential partners. A cDNA clone was identified which produced a protein in yeast that interacted with Xenopus TFIIIA but not with yeast TFIIIA. This rat clone was sequenced and the primary structure of the human homolog (termed TFIIIA-intP for TFIIIA-interacting protein) was determined from expressed sequence tags. In vitro interaction of recombinant human TFIIIA-intP with recombinant Xenopus TFIIIA was demonstrated by immunoprecipitation of the complex using anti-TFIIIA-intP antibody. Interaction of rat TFIIIA with rat TFIIIA-intP was indicated by co-chromatography of the two proteins on DEAE-5PW following fractionation of a rat liver extract on cation, anion and gel filtration resins. In a HeLa cell nuclear extract, recombinant TFIIIA-intP was able to stimulate TFIIIA-dependent transcription of the Xenopus 5S ribosomal RNA gene but not TFIIIA-independent transcription of the human adenovirus VA RNA gene.
PMCID: PMC103300  PMID: 10756201

Results 1-2 (2)