The cytotoxic T lymphocyte antigen-4 is a major Graves' disease locus
| Autor: | Anthony Toft, Pat Kendall-Taylor, E. T. Young, David M. Large, Helen Imrie, David Carr, Petros Perros, Bijayeswar Vaidya, William F. Kelly, Mark I. McCarthy, Simon H. S. Pearce |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Immunoconjugates Genetic Linkage Graves' disease Population Locus (genetics) Major histocompatibility complex Autoimmune Diseases Abatacept Major Histocompatibility Complex Gene mapping Antigen Antigens CD Genetics medicine Humans CTLA-4 Antigen Allele education Molecular Biology Genetics (clinical) education.field_of_study biology General Medicine medicine.disease Antigens Differentiation Graves Disease Thyroid disorder Haplotypes Chromosomes Human Pair 2 biology.protein Chromosomes Human Pair 6 Female |
| Zdroj: | Human Molecular Genetics. 8:1195-1199 |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/8.7.1195 |
| Popis: | Graves' disease (GD) is an autoimmune thyroid disorder that is inherited as a complex trait. We have genotyped 77 affected sib-pairs with autoimmune thyroid disease for eight polymorphic markers spanning the cytotoxic T lymphocyte antigen-4 ( CTLA-4 ) region of chromosome 2q31-q33, and for five markers spanning the major histocompatibility complex ( MHC ) region of chromosome 6p21. Non-parametric analysis showed linkage of GD to the CTLA-4 region with a peak non-parametric linkage (NPL) score of 3.43 ( P = 0.0004) at the marker D2S117. The proportion of affected full-sibs sharing zero alleles (z0) reached a minimum of 0.113 close to D2S117, giving a locus-specific lambdas for this region of 2.2. Families with brother-sister sib-pairs showed a peak NPL of 3.46 ( P = 0.0003, lambdas > 10) at D2S117, compared with 2.00 ( P = 0.02, lambdas = 1.9) in the families with only affected females, suggesting a stronger influence in families with affected males. Association between GD and the G allele of the Thr17Ala polymorphism within the CTLA-4 gene ( CTLA4A/G ) was observed using unaffected sib controls ( P = 0.005). Lesser evidence for linkage was found at the MHC locus, with a peak NPL score of 1.95 ( P = 0.026), between the markers D6S273 and TNFalpha. We demonstrate that the CTLA-4 locus (lambdas = 2.2) and the MHC locus (lambdas = 1.6) together confer approximately 50% of the inherited susceptibility to GD disease in our population. |
| Databáze: | OpenAIRE |
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