ABSTRACT
Polymorphism in transporter associated with antigen processing (TAP)1 gene has been observed in African American Graves' disease patients. Single strand conformational polymorphism has been used to identify variation for the locus. First-strand cDNA was generated from cell lines obtained by Epstein-Barr virus immortalization. Four variant alleles for TAP1 have been observed and the products have been sequenced to compare with the location of observed with SSCP position patterns. Variants were detected and compared with substitutions within TAP1 polypeptide which includes changing valine to leucine and three (3) silent substitutions for glycine, glutamic acid and alanine.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Black People/genetics , Graves Disease/genetics , Polymorphism, Single-Stranded Conformational , ATP Binding Cassette Transporter, Subfamily B, Member 2 , Adult , Alleles , Base Sequence , DNA, Single-Stranded/analysis , Genetic Variation , Humans , Major Histocompatibility Complex , Middle Aged , Molecular Sequence Data , Polymerase Chain Reaction/methodsABSTRACT
HLA heterogeneity occurs in various ethnic groups and has been significantly associated with Graves' disease. In this study we have determined that DQ3 is associated with Graves' disease in African-Americans. Human leukocyte antigen (HLA) typing of D-region antigens in 139 controls and 45 Graves' disease patients reveals significant differences for HLA-DR2, DR9, DQ1, and DQ3. The latter remained significant after correction. Increases in HLA-DR9 and DR3 are associated with increases in DQ3 and DQ2, respectively. The decrease in DR2 is associated with a decrease in DQ1. The associated increases and decreases in DR with DQ antigens probably reflect linkage disequilibrium. Patients were evaluated for autoantibodies against microsomal antigens and/or against thyroglobulin. All of the normal control volunteers were negative for thyroid antibodies and thirteen percent of patients produced autoantibodies. No significant associations were detected for antibody production, type of treatment required, age of onset, family history of Graves', status of T3, T4 levels, goiter and/or ophthalmopathy.
