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THE ROLE OF T CELL RECEPTOR Vβ GENE POLYMORPHISMS IN SUSCEPTIBILITY TO JUVENILE RHEUMATOID ARTHRITIS

Brzezinski, Jennifer Lynn
http://rave.ohiolink.edu/etdc/view?acc_num=ucin997381866

Abstract Details

2001, PhD, University of Cincinnati, Medicine : Molecular Genetics, Biochemistry and Microbiology.
Juvenile rheumatoid arthritis is the most common childhood rheumatic disease. Previous studies have shown that null alleles of the T cell receptor Vβ (TCRBV) gene segment TCRBV6S1 are associated with some subsets of JRA, namely polyarticular JRA. Linkage disequilibrium has been identified between the null alleles of TCRBV6S1 and alleles of the neighboring TCRBV genes TCRBV5S5P, TCRBV1S1 and TCRBV13S5, and this genetic association may therefore be due to a linked susceptibility locus. In Caucasian individuals, only three of the possible 12 haplotypes were represented, and the two TCRBV6S1 null alleles are present on distinct haplotypes. However, in additional ethnic groups significant deviations in the patterns of linkage disequilibrium were observed. This needs to be taken into account in any genetic studies involving TCR polymorphisms. TCRBV repertoire analysis was undertaken in an effort to establish a functional role for TCRBV6S1 null allele haplotypes in the pathogenesis of JRA. TCRBV1S1 is the only member of this haplotype that is readily expressed in the peripheral repertoire; analysis of synovial and peripheral blood TCRBV1S1 repertoires revealed an allelic bias wherein TCRBV1S1A2 is under-represented in heterozygotes. Additionally, individuals who are carriers of TCRBV1S1A2 have lower levels of TCRBV1S1 mRNA and reduced numbers of Vβ1 + T cells. Although we have not definitively established a role for TCRBV1S1A2 in JRA, reduced numbers of Vβ1 + T cells may nonetheless be relevant to disease pathogenesis. The transmission disequilibrium test (TDT) was used to test whether TCRBV6S1 null alleles are preferentially transmitted to JRA probands. Unexpectedly, the TDT demonstrates under-transmission of TCRBV6S1 null alleles to polyarticular JRA patients, suggesting these alleles may be protective. In fact, the two null alleles do not appear to contribute equally to disease protection in all JRA subtypes. Although this data is preliminary, it suggests that caution must be observed when interpreting the results of case-control studies that are sensitive to population stratification events. Although case-control and TDT studies have produced decidedly opposing results, there is evidence nonetheless that TCRBV6S1 null alleles may have an important role in the genetic component of JRA.
Edmund Choi (Advisor)
Biology, Genetics
TCR; JUVENILE RHEUMATOID ARTHRITIS; POLYMORPHISM; HAPLOTYPE

Recommended Citations

Citations

  • Brzezinski, J. L. (2001). THE ROLE OF T CELL RECEPTOR Vβ GENE POLYMORPHISMS IN SUSCEPTIBILITY TO JUVENILE RHEUMATOID ARTHRITIS [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin997381866

    APA Style (7th edition)

  • Brzezinski, Jennifer. THE ROLE OF T CELL RECEPTOR Vβ GENE POLYMORPHISMS IN SUSCEPTIBILITY TO JUVENILE RHEUMATOID ARTHRITIS. 2001. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin997381866.

    MLA Style (8th edition)

  • Brzezinski, Jennifer. "THE ROLE OF T CELL RECEPTOR Vβ GENE POLYMORPHISMS IN SUSCEPTIBILITY TO JUVENILE RHEUMATOID ARTHRITIS." Doctoral dissertation, University of Cincinnati, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin997381866

    Chicago Manual of Style (17th edition)

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