title: CDS1 and promoter single nucleotide polymorphisms of the CTLA-4 gene in human myasthenia gravis.
abstract: The cytotoxic T lymphocyte associated protein 4 (CTLA-4) gene (Ctla-4) is a candidate gene for autoimmune disease. We here report results of two single nucleotide polymorphisms (SNPs) in the Ctla-4, a +49 A/G SNP in CDS1 and a C/T promoter SNP at position -318. There were no differences in these two SNPs between patients and healthy individuals. The frequency of allele G and genotype G/G at position +49 in CDS1 was increased in patients with thymoma when compared with patients with normal and hyperplastic thymic histopathology. Patients with the G/G genotype had signs of immune activation manifested as higher levels of serum IL-1beta and higher percentage of CD28(+) T lymphocytes. There was a strong linkage between the 86bp allele in the 3'-UTR and the A(+49) allele in CDS1. Our results suggest that the SNP at position +49 in CDS1 might be associated with the manifestations of MG.
authors.affiliation: Immunological Research Unit, Center for Molecular Medicine and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: X B
authors.initials: XB
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Kakoulidou
authors.forename: Q
authors.initials: Q
authors.lastname: Qiu
authors.forename: R
authors.initials: R
authors.lastname: Giscombe
authors.forename: DeRen
authors.initials: D
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Pirskanen
authors.forename: A K
authors.initials: AK
authors.lastname: Lefvert
mesh_terms: D020413:3' Untranslated Regions; D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D018106:CD28 Antigens / Q000032:analysis; D060908:CTLA-4 Antigen; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D018796:Immunoconjugates; D007375:Interleukin-1 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015810:Linkage Disequilibrium; D008297:Male; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013548:Sweden; D013601:T-Lymphocytes / Q000276:immunology; D013945:Thymoma / Q000235:genetics; D013952:Thymus Hyperplasia / Q000235:genetics; D013953:Thymus Neoplasms / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007375:Interleukin-1; D018664:Interleukin-12; D000069594:Abatacept