HLA-B5801遗传标记.pptVIP

HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol研发部 张艳 别嘌呤醇作用 Patients and Control Subjects Recruitment 228 control individuals： (135 allopurinol-tolerant subjects 93 healthy subjects） 51 patients with allopurinol–SCAR SNP Genotyping A total of 823 SNPs： 197 SNPs from 4Mb of the MHC region 626 SNPs selected from genes encoding immune-related molecules and drug metabolizing enzymes HLA Genotyping HLA alleles A, B, C, and DRB1, were determined by sequence-specific oligonucleotide reverse lineblot Potential ambiguities were resolved by sequencing-based typing Statistical Analysis Categorical data were compared between groups with use of Fisher’s exact tests, and continuous data(presented as median, with range given in parentheses) were compared with use of t tests. All P values were two-tailed; a P value of 0.05 was considered to indicate statistical significance. Allelic association screen was carried out by the Cochran– Armitage Trend test for each SNP . Odds ratios were calculated with Haldane’s modification, which adds 0.5 to all cells to accommodate possible zero counts . The corrected P (Pc) values were adjusted by using Bonferroni’s correction for multiple comparisons to account for the observed alleles (17 for HLA-A, 40 for HLA-B, 19 for HLA-C, and 30 for HLA-DRB1). Therefore, the Pc values were multiplied by a factor of 387,600. Characteristics of Patients and Controls Association Screen for Candidate Gene SNPs HLA Allele Frequency Discussion In fact, the association is 100% in that the HLA-B allele B*5801 was present in all 51 patients with allopurinol-induced SCAR, with an odds ratio exceeding that reported for the association between HLAB27 and ankylosing spondylitis genotyping the B*5801 allele may provide a better guidance of avoiding allopurinol-induced SCAR in patients with renal insufficiency than dosage adjusting. This study, together with the previous reports, s