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T-cell receptor chain germline gene polymorphisms in multiple sclerosis

From the Center for BioTechnology (Drs. Hillert, Leng, and Olerup), Karolinska Institute, NOVUM, Huddinge, Sweden; the Departments of Neurology (Drs. Hillert and Leng) and Clinical Immunology (Dr. Olerup), Karolinska Institute at Huddinge Hospital, Huddinge, Sweden.

It has been proposed that genetic predisposition to multiple sclerosis (MS) and other diseases with autoimmune features is conferred by T-cell receptor (TcR) genes in addition to HLA class II genes. Although a family study has suggested linkage of susceptibility to MS to TcR genes, reports of disease associations with restriction fragment length polymorphism (RFLPI-defined alleles of TcR genes have been difficult to confirm, including a report of association of MS with TcR ß-chain gene RFLPs. We report here the distribution of three sets of RFLPs of the TcR chain genes. Similar frequencies in patients and controls were observed for TaqI and Bgl II RFLPs of the TcR constant segment (C), the latter earlier reported to be associated with MS. A previously reported MS-associated PssI RFLP of the V12 and C gene segments could not be confirmed. Our results indicate that these seemingly polymorphic restriction fragments are possibly the results of incomplete enzymatic cleavage of DNA in the RFLP analysis. We conclude that no convincing evidence exists for the association of MS with RFLPs of the TcR or ß chain genes.

Address correspondence and reprint requests to Dr. Jan Hillert, Center for Bio Technology, Karolinska Institute, NOVUM, S-141 57, Huddinge, Sweden.

Supported by grants from the Swedish Medical Research Council (project nos. 08709, 00793, and 08890), Swedish Association of the Neurologically Disabled, Sigurd and Elsa Golje Memorial Foundation, Swedish Society of Medicine, Swedish Society for Medical Research, OE and Edla Johanssons Vetenskapliga Stiftelse, Karolinska Institute, Soderhergs Foundations, Lars Hierta Memorial Foundation, Anders Otto Swards Foundation, and Marcus Borgstrom Foundation.

Received April 18, 1991. Accepted for publication in final form July 2, 1991

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