OBJECTIVES: To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to ankylosing spondylitis (AS) and rheumatoid arthritis (RA), or linked with any specific clinical or familial features of the two conditions. METHODS: CYP2D6 genotypes were determined in 54 patients with AS, 53 patients with RA, and 662 healthy controls. Leucocyte DNA was analysed for the presence of mutations by restriction fragment length polymorphism analysis with the restriction enzyme Xbal and by two separate polymerase chain reaction assays. RESULTS: On the basis of odds ratio (OR), individuals with two inactive CYP2D6 alleles were more susceptible to AS than controls (OR 2.71, 95% confidence interval (CI) 1.04 to 7.08), with a stronger effect for the CYP2D6B allele (OR 4.11, 95% CI 1.54 to 11.0). No significant differences in the distribution of overall genotypes and allele frequencies were observed between RA and controls. No significant relationships were found between the skeletal, extraskeletal or familial features of AS or RA (iritis, psoriasis, inflammatory enteropathy and rheumatoid nodules, kerato-conjunctivitis sicca, pleuritis, rheumatoid and antinuclear factors) and the overall genotype. CONCLUSIONS: Our findings suggest a modest association between homozygosity for inactive CYP2D6 alleles, particularly CYP2D6B alleles, and susceptibility to AS. However, our results fail to demonstrate a genetic link between CYP2D6 genotype and RA.
OBJECTIVES: To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to ankylosing spondylitis (AS) and rheumatoid arthritis (RA), or linked with any specific clinical or familial features of the two conditions. METHODS:CYP2D6 genotypes were determined in 54 patients with AS, 53 patients with RA, and 662 healthy controls. Leucocyte DNA was analysed for the presence of mutations by restriction fragment length polymorphism analysis with the restriction enzyme Xbal and by two separate polymerase chain reaction assays. RESULTS: On the basis of odds ratio (OR), individuals with two inactive CYP2D6 alleles were more susceptible to AS than controls (OR 2.71, 95% confidence interval (CI) 1.04 to 7.08), with a stronger effect for the CYP2D6B allele (OR 4.11, 95% CI 1.54 to 11.0). No significant differences in the distribution of overall genotypes and allele frequencies were observed between RA and controls. No significant relationships were found between the skeletal, extraskeletal or familial features of AS or RA (iritis, psoriasis, inflammatory enteropathy and rheumatoid nodules, kerato-conjunctivitis sicca, pleuritis, rheumatoid and antinuclear factors) and the overall genotype. CONCLUSIONS: Our findings suggest a modest association between homozygosity for inactive CYP2D6 alleles, particularly CYP2D6B alleles, and susceptibility to AS. However, our results fail to demonstrate a genetic link between CYP2D6 genotype and RA.
Authors: C A Smith; A C Gough; P N Leigh; B A Summers; A E Harding; D M Maraganore; S G Sturman; A H Schapira; A C Williams; D M Maranganore Journal: Lancet Date: 1992-06-06 Impact factor: 79.321
Authors: C R Wolf; C A Smith; A C Gough; J E Moss; K A Vallis; G Howard; F J Carey; K Mills; W McNee; J Carmichael Journal: Carcinogenesis Date: 1992-06 Impact factor: 4.944
Authors: F C Arnett; S M Edworthy; D A Bloch; D J McShane; J F Fries; N S Cooper; L A Healey; S R Kaplan; M H Liang; H S Luthra Journal: Arthritis Rheum Date: 1988-03
Authors: Won-Tae Chung; Jung-Yoon Choe; Won Cheoul Jang; Su Min Park; Young Chang Ahn; Il Kyu Yoon; Tae-Hwan Kim; Youn-Hyoung Nam; Sung-Hoon Park; Sung-Won Lee; Seong-Kyu Kim Journal: Rheumatol Int Date: 2010-03-28 Impact factor: 2.631
Authors: S H Laval; A Timms; S Edwards; L Bradbury; S Brophy; A Milicic; L Rubin; K A Siminovitch; D E Weeks; A Calin; B P Wordsworth; M A Brown Journal: Am J Hum Genet Date: 2001-02-27 Impact factor: 11.025