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

Objective, Signaling molecules from the T cell receptor zeta/Fc epsilon rec eptor gamma (TCR zeta/FcR gamma) family play a critical role in the functio n of Fc gamma 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 TCR zeta i n systemic lupus erythematosus (SLE). Methods, We amplified the whole coding region of TCR zeta by reverse transc riptase-polymerase chain reaction (PCR) and directly sequenced the PCR prod ucts with a dye primer technique to facilitate heterozygote detection. Results. An alternative splicing form of TCR zeta, with a CAG codon (glutam ine) inserted at the splice junction of exons 4 and 5, was found both in SL E and in non-SLE subjects. Both splice isoforms of TCR zeta occurred in hum an mixed peripheral blood mononuclear cells, natural killer cells, and Jurk at T cells. in TCR zeta, 2 silent and 2 missense mutations were found, but neither coding change occurred in the immunoreceptor tyrosine-activation mo tif, No unique mutations were found in Caucasian, African American, Hispani c, Chinese, or Japanese SLE patients living in North America. Conclusion. The uncommon and equal occurrence of novel single-nucleotide po lymorphisms in both SLE patients and normal subjects makes it improbable th at they play important roles in genetic susceptibility to SLE.