Abstract
Objective: To examine the association between single nucleotide polymorphisms (SNPs) in the human CIITA gene (MHC2TA) and SLE.
Methods: Promoters and coding regions of MHC2TA were evaluated for polymorphisms in 100 patients with SLE and 100 healthy donors. Eight oligonucleotide primer sets that covered the coding region and each promoter region were used for genomic analysis of SNPs.
Results: Allele frequencies of previously reported SNPs did not differ between healthy donors and patients with SLE. Additionally, a new polymorphism in an intronic region at nt 485 (A→A/G) was identified, which is close to the polymorphism at nt 474 that has been associated with one of the disease causing CIITA cDNA mutations in bare lymphocyte syndrome. This SNP was found in 11% of patients with SLE and in 3% of healthy donors, suggesting it may have a role in the pathogenesis of SLE.
Conclusions: A newly identified polymorphism in an intronic region at nt 485 (A→A/G) may have an important role in the pathogenesis of SLE.
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Figure 1.
SNPs in MHC2TA pIII and coding region. (A) Genomic DNA was isolated from peripheral blood mononuclear cells, and PCR and direct sequencing were performed with eight oligonucleotide primer sets for genomic analysis of SNPs (arrows). (B) MHC2TA promoter elements and exon organisation. Arrows on the box represent upstream regulatory sequences for each promoter. Promoter pI is used primarily by dendritic cells, pIII by B cells, and pIV for IFNγ-inducible CIITA expression by non-professional APCs.
Figure 2.
(A) SNP at nt 485 near a splice site (nt 474) of the MHC2TA gene and allele frequency in patients with SLE. A χ2 test for independence indicated that p = 0.0266 between these two groups. (B) mRNA transcripts with and without the SNP at nt 485. An RT-PCR was performed as described in the "Patients and methods" section. PCR products were analysed with 3% agarose gels. Arrow indicates the expected band.