Single-nucleotide polymorphisms of T cell receptor ζ chain in patients with systemic lupus erythematosus

Objective. Signaling molecules from the T cell receptor ζ/Fcε receptor γ (TCRζ/FcRγ) family play a critical role in the function of Fcγ receptors and the TCR and are located on human chromosome 1, where lupus susceptibility genes are located. This study was undertaken to investigate the possibility of polymorphisms and/or mutations of TCRζ in systemic lupus erythematosus (SLE). Methods. We amplified the whole coding region of TCRζ by reverse transcriptase-polymerase chain reaction (PCR) and directly sequenced the PCR products with a dye primer technique to facilitate heterozygote detection. Results. An alternative splicing form of TCRζ, with a CAG codon (glutamine) inserted at the splice junction of exons 4 and 5, was found both in SLE and in non-SLE subjects. Both splice isoforms of TCRζ occurred in human mixed peripheral blood mononuclear cells, natural killer cells, and Jurkat T cells. In TCRζ, 2 silent and 2 missense mutations were found, but neither coding change occurred in the immunoreceptor tyrosine- activation motif. No unique mutations were found in Caucasian, African American, Hispanic, Chinese, or Japanese SLE patients living in North America. Conclusion. The uncommon and equal occurrence of novel single- nucleotide polymorphisms in both SLE patients and normal subjects makes it improbable that they play important roles in genetic susceptibility to SLE.