Background Gout is caused by chronic elevation of serum uric acid levels above the saturation point for monosodium urate crystal formation. Allopurinol, which can inhibit xanthine oxidase and decrease the formation of uric acid, is widely used as a primary therapy for the treatment chronic gout and hyperuricemia in China. However, some patients may develop allopurinol-induced life-threating severe cutaneous adverse reaction (SCAR). Hung and colleagues  in Taiwan reported a strong association between HLA-B*5801 and allopurinol-induced SCAR, and replicated by following studies in different areas and countries, including China . Previously, Tohkin and colleagues  in Japan carried out a genome wide association study (GWAS) and indicates that rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SCAR, is in absolute linkage disequilibrium (LD) with HLA-B*5801. Rs9263726 is expected to substitute HLA-B*5801 genotyping in clinical application for predicting the onset of allopurinol-induced SCAR.
Objectives To investigate the allele frequency of rs9263726 in patients with gout or hyperuricemia as well as healthy volunteers from South China. Compare clinical characteristics between different genotype of rs9263726.
Methods We enrolled 171 patients with gout or hyperuricemia which was diagnosed by clinicians. And 191 healthy volunteers with age and sex match were taken as controls in this study. Blood samples were collected and DNA samples were extracted. A pair of specific primers were employed to perform PCR amplification. All PCR products were carried out a Sanger sequencing.
Results Genotype frequencies for rs9263726 polymorphism observed were G/G (88.89%), G/A (9.36%), A/A (1.75%) in patients with gout or hyperuricemis. Rs9263726 A allele was observed in 11.11% of patients, whereas the allele frequency was 6.43%. While in healthy volunteers group, 12.57% was carried rs9263726 A allele, whereas the allele frequency was 7.07%. There was no significant differences between the two groups when compared with the carried rate of rs9263726A allele. Patients were divided into two groups based on whether they carried rs9263726A allele or not. The mean uric acid level is (435.89±129.80)μmol/L in rs9263726A allele group and (419.84±139.45) μmol/L in rs9263726G allele. No significant difference was observed when compared the age, genders as well as uric acid level.
Conclusions The frequency of rs9263726 A allele is relatively high in South China. There is no evidence that the frequency of rs9263726A allele is different in patients with gout or hyperuricemis and healthy volunteers. Further studies should carried out to explore the relationship between rs9263726A allele and allopurinol-related SCAR as well as HLA-B*5801.
Hung SI, Chung WH, Liou LB, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005. 102(11): 4134–9.
Cao ZH, Wei ZY, Zhu QY, et al. HLA-B*58:01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese. Pharmacogenomics. 2012. 13(10): 1193–201.
Tohkin M, Kaniwa N, Saito Y, et al. A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Pharmacogenomics J. 2013. 13(1): 60–9.
Disclosure of Interest X. Li: None declared, Q. Li Grant/research support from: The National Natural Science Foundation of China, J. Gu Grant/research support from: The National Natural Science Foundation of China, Z. Chen Grant/research support from: The National Natural Science Foundation of China