Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis
Brown, Matthew A., Edwards, S., Hoyle, E., Campbell, S., Laval, S., Daly, A. K., Pile, K. D., Calin, A., Ebringer, A., Weeks, D. E., & Wordsworth, B. P. (2000) Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis. Human Molecular Genetics, 9(11), pp. 1563-1566.
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 (CYP2D64) was not associated with increased susceptibility to AS. Significant within-family association of CYP2D64 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.
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|Item Type:||Journal Article|
|Additional Information:||Cited By :70
Export Date: 21 September 2015
Correspondence Address: Brown, M.A.; Wellcome Trust Centre Human Genetics, Roosevelt Drive, Headington, Oxon. OX3 7BN, United Kingdom; email: firstname.lastname@example.org
|Keywords:||debrisoquine 4 hydroxylase, allele, ankylosing spondylitis, article, case control study, chromosome 22, controlled study, DNA polymorphism, family, genetic association, genetic linkage, genetic risk, heterozygosity, homozygosity, human, major clinical study, phenotype, priority journal, recurrence risk, Alleles, Case-Control Studies, Cytochrome P-450 CYP2D6, DNA, Family Health, Female, Genetic Predisposition to Disease, Genotype, Humans, Linkage (Genetics), Lod Score, Male, Nuclear Family, Polymorphism, Genetic, Spondylitis, Ankylosing|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||© 2000 Oxford University Press|
|Deposited On:||27 Oct 2015 01:43|
|Last Modified:||27 Oct 2015 01:43|
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