Toggle Main Menu Toggle Search

Open Access padlockePrints

Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis

Lookup NU author(s): Sandra Campbell, Dr Steven Laval, Professor Ann DalyORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.

Publication metadata

Author(s): Daly AK; Campbell S; Laval S; Brown MA; Edwards S; Hoyle E; Pile KD; Calin A; Ebringer A; Weeks DE; Wordsworth BP

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2000

Volume: 9

Issue: 11

Pages: 1563-1566

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press


DOI: 10.1093/hmg/9.11.1563


Altmetrics provided by Altmetric