Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis.
Ankylosing spondylitis (AS) is a common and highly familial rheumatic disorder. The sibling recurrence risk ratio for the disease is 63 and heritability assessed in twins >90%. Although MHC genes, including HLA-B27, contribute only 20-50% of the genetic risk for the disease, no non-MHC gene h...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2000
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| _version_ | 1797079257860538368 |
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| author | Brown, M Edwards, S Hoyle, E Campbell, S Laval, S Daly, A Pile, K Calin, A Ebringer, A Weeks, D Wordsworth, B |
| author_facet | Brown, M Edwards, S Hoyle, E Campbell, S Laval, S Daly, A Pile, K Calin, A Ebringer, A Weeks, D Wordsworth, B |
| author_sort | Brown, M |
| collection | OXFORD |
| description | Ankylosing spondylitis (AS) is a common and highly familial rheumatic disorder. The sibling recurrence risk ratio for the disease is 63 and heritability assessed in twins >90%. Although MHC genes, including HLA-B27, contribute only 20-50% of the genetic risk for the disease, no non-MHC gene has yet been convincingly demonstrated to influence either susceptibility to the disease or its phenotypic expression. Previous linkage and association studies have suggested the presence of a susceptibility gene for AS close to, or within, the cytochrome P450 2D6 gene (CYP2D6, debrisoquine hydroxylase) located at chromosome 22q13.1. We performed a linkage study of chromosome 22 in 200 families with AS affected sibling-pairs. Association of alleles of the CYP2D6 gene was examined by both case-control and within-family means. For case-control studies, 617 unrelated individuals with AS (361 probands from sibling-pair and parent-case trio families and 256 unrelated non-familial sporadic cases) and 402 healthy ethnically matched controls were employed. For within-family association studies, 361 families including 161 parent-case trios and 200 affected sibling-pair families were employed. Homozygosity for poor metabolizer alleles was found to be associated with AS. Heterozygosity for the most frequent poor metabolizer allele (CYP2D6*4) was not associated with increased susceptibility to AS. Significant within-family association of CYP2D6*4 alleles and AS was demonstrated. Weak linkage was also demonstrated between CYP2D6 and AS. We postulate that altered metabolism of a natural toxin or antigen by the CYP2D6 gene may increase susceptibility to AS. |
| first_indexed | 2024-03-07T00:43:13Z |
| format | Journal article |
| id | oxford-uuid:83c54e55-5740-45eb-8f78-9d96d15e46e2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:43:13Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:83c54e55-5740-45eb-8f78-9d96d15e46e22022-03-26T21:46:26ZPolymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:83c54e55-5740-45eb-8f78-9d96d15e46e2EnglishSymplectic Elements at Oxford2000Brown, MEdwards, SHoyle, ECampbell, SLaval, SDaly, APile, KCalin, AEbringer, AWeeks, DWordsworth, BAnkylosing spondylitis (AS) is a common and highly familial rheumatic disorder. The sibling recurrence risk ratio for the disease is 63 and heritability assessed in twins >90%. Although MHC genes, including HLA-B27, contribute only 20-50% of the genetic risk for the disease, no non-MHC gene has yet been convincingly demonstrated to influence either susceptibility to the disease or its phenotypic expression. Previous linkage and association studies have suggested the presence of a susceptibility gene for AS close to, or within, the cytochrome P450 2D6 gene (CYP2D6, debrisoquine hydroxylase) located at chromosome 22q13.1. We performed a linkage study of chromosome 22 in 200 families with AS affected sibling-pairs. Association of alleles of the CYP2D6 gene was examined by both case-control and within-family means. For case-control studies, 617 unrelated individuals with AS (361 probands from sibling-pair and parent-case trio families and 256 unrelated non-familial sporadic cases) and 402 healthy ethnically matched controls were employed. For within-family association studies, 361 families including 161 parent-case trios and 200 affected sibling-pair families were employed. Homozygosity for poor metabolizer alleles was found to be associated with AS. Heterozygosity for the most frequent poor metabolizer allele (CYP2D6*4) was not associated with increased susceptibility to AS. Significant within-family association of CYP2D6*4 alleles and AS was demonstrated. Weak linkage was also demonstrated between CYP2D6 and AS. We postulate that altered metabolism of a natural toxin or antigen by the CYP2D6 gene may increase susceptibility to AS. |
| spellingShingle | Brown, M Edwards, S Hoyle, E Campbell, S Laval, S Daly, A Pile, K Calin, A Ebringer, A Weeks, D Wordsworth, B Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis. |
| title | Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis. |
| title_full | Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis. |
| title_fullStr | Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis. |
| title_full_unstemmed | Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis. |
| title_short | Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis. |
| title_sort | polymorphisms of the cyp2d6 gene increase susceptibility to ankylosing spondylitis |
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