Tsan Teng Ou

Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study

Objective To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. Design National prospective cohort study. Setting 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. Participants 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants’ peripheral blood was used to assess the presence of HLA-B*58:01. Main outcome measures Incidence of allopurinol induced SCARs with and without screening. Results Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). Conclusions Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

Manganese superoxide dismutase and cytochrome P450 1A1 genes polymorphisms in rheumatoid arthritis in Taiwan

To investigate the role of manganese superoxide dismutase (MnSOD) and cytochrome P450 1A1 (CYP1A1) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan, MnSOD and CYP1A1 genes polymorphisms were determined by he polymerase chain reaction/restriction fragment length polymorphism method in 112 patients with RA and 96 controls. There were no significant differences in the genotype, allele, and phenotype frequencies of MnSOD Ala-9Val (C1183T) polymorphisms between patients with RA and controls. The polymorphism of MnSOD 5777T, threonine at the 58th amino acid, cannot be found in RA patients and controls in Taiwan. The allele and phenotype frequencies of CYP1A1 4887A and genotype frequency of CYP1A1 4887C/A were lower in RA patients than in controls, whereas the significant difference was lost after correction. MnSOD C1183T polymorphisms were not associated with the clinical manifestations of RA. However, RA patients with CYP1A1 4889G/G have significantly higher frequency of Sjögrens syndrome, especially in the presence of MnSOD 1183T/T. Patients with CYP1A1 4887C/A also have a trend to develop Sjögrens syndrome in the presence of MnSOD 1183T/T. The linkage disequilibrium between CYP1A1 4889G and CYP1A1 6235C can be found in this study. MnSOD gene polymorphisms are not related to susceptibility to RA in Taiwan, whereas individuals with CYP1A1 4887A tend to avoid the development of RA. Moreover, CYP1A1 4889G/G and 4887C/A may play a role in the development of Sjögrens syndrome, especially in the presence of MnSOD 1183T/T. These findings are preliminary. A further confirmation study is necessary.

Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in ankylosing spondylitis

OBJECTIVES To investigate the associations of cytochrome p450 1A1 (CYP1A1) and manganese superoxide dismutase (MnSOD) genes polymorphisms with the susceptibility to AS in Taiwan. METHODS The polymorphisms of CYP1A1 and MnSOD genes were determined in 70 patients with ankylosing spondylitis (AS) and 93 healthy controls by polymerase chain reaction (PCR)/restriction fragment length polymorphisms (RFLP) methods. RESULTS The genotype frequency of CYP1A1 4887C/A was significantly lower in patients with AS than in controls. The phenotype frequency of CYP1A1 4887A also tended to be decreased in patients with AS. There were no significant differences in the genotype, allele, and phenotype frequencies of MnSOD gene polymorphisms between patients with AS and controls. CONCLUSION CYP1A1 4887A may be a protective factor for the development of AS in Taiwan. However, MnSOD gene polymorphisms are not associated with the susceptibility to AS.

Cytochrome P450 and manganese superoxide dismutase genes polymorphisms in systemic lupus erythematosus

OBJECTIVES To investigate the role of cytochrome P450 1A1 (CYP1A1) and manganese superoxide dismutase (Mn SOD) genes polymorphisms in the pathogenesis of systemic lupus erythematosus (SLE) in Taiwan. METHODS CYP1A1 and Mn SOD genes polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism (RFLP) method in 90 patients with SLE and 94 healthy controls. RESULTS The genotype frequency of CYP1A1 4887C/A was significantly higher in patients with SLE than in controls. The allele and phenotype frequencies of CYP1A1 4887A were also significantly increased in SLE patients. In contrast, there were no significant differences in the genotype, allele and phenotype frequencies of Mn SOD C1183T polymorphisms between patients with SLE and controls. We also found that SLE patients with CYP1A1 4887A had a trend of increasing prevalence of renal involvement, while Mn SOD C1183T polymorphisms were not associated with the renal involvement in SLE. CONCLUSIONS CYP1A1 4887A may be a precipitating factor for the development of SLE. It also tended to be associated with the occurrence of renal involvement in SLE patients. A synergistic effect was found between CYP1A1 4887C/A and Mn SOD 1183T/T on the susceptibility to SLE.

Manganese superoxide dismutase gene polymorphisms in psoriatic arthritis

The purpose of the present study is to investigate the role of manganese superoxide dismutase (MnSOD) gene polymorphisms in the susceptibility to psoriatic arthritis. MnSOD gene polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphisms method in fifty-two patients with psoriatic arthritis and 90 healthy controls. The genotype frequency of MnSOD 1183C/T was significantly higher in patients with psoriatic arthritis than in controls. In contrast, the frequency of MnSOD 1183T/T was significantly decreased in patients with psoriatic arthritis. The phenotype frequency of MnSOD 1183C was significantly increased in patients with psoriatics arthritis in comparison to healthy controls. Therefore, MnSOD 1183C polymorphisms may be a precipitating factor for the development of psoriatic arthritis.