Detection of HLA-B*58:01 with TaqMan assay and its association with allopurinol-induced sCADR

Xinju Zhang; Huili Ma; Chunying Hu; Bo Yu; Weizhe Ma; Zhiyuan Wu; Xiaoqun Luo; Hejian Zou; Ming Guan

doi:10.1515/cclm-2014-0251

Article

Detection of HLA-B58:01* with TaqMan assay and its association with allopurinol-induced sCADR

Xinju Zhang , Huili Ma , Chunying Hu , Bo Yu , Weizhe Ma , Zhiyuan Wu , Xiaoqun Luo , Hejian Zou and Ming Guan

Published/Copyright: September 26, 2014

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information

From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 53 Issue 3

Abstract

Background: The HLA-B*58:01 allele is associated with allopurinol-induced severe cutaneous adverse drug reactions (sCADR) in certain geographic regions, but the diversity of the correlation is large. In addition, the currently available HLA-B*58:01 testing methods are too laborious for use in routine clinical detection. The objective of this study was to develop a new, convenient method for the detection of HLA-B*58:01 and to investigate the association of HLA-B*58:01 with allopurinol-induced sCADR in a Han Chinese population.

Methods: A new method combining sequence-specific primers (SSP) and TaqMan probe amplification was developed in this study and was used to detect the HLA-B*58:01 in 48 allopurinol-induced sCADR, 133 allopurinol-tolerant, and 280 healthy individuals. The accuracy, sensitivity, and specificity were assessed by a commercial PCR-SSP HLA-B typing kit. The low limit of detection was detected by serial dilution of an HLA-B*58:01-positive DNA template.

Results: The new method successfully identified HLA-B*58:01 in thousands of HLA-B alleles, and the results for 344 DNA samples were perfectly concordant with the results of the commercial PCR-SSP HLA-B kit. The analytical sensitivity is 100% and the specificity is over 99%. The low limit of detection of this assay is 100 pg DNA, which was 10 times more sensitive than the commercial PCR-SSP kit. HLA-B*58:01 was present in 93.8% of the patients with sCADR, 7.5% of the allopurinol-tolerant patients, and 12.1% of the healthy controls. The frequency of HLA-B*58:01 was significantly higher in the sCADR group than in the control group (p<0.0001). However, there was no significant difference between the allopurinol-tolerant and control groups (p=0.1547).

Conclusions:HLA-B*58:01 has a strong association with allopurinol-induced sCADR in Han Chinese. The newly developed method is reliable for HLA-B*58:01 detection prior to allopurinol therapy.

Keywords: allopurinol; HLA-B*58:01; severe cutaneous adverse drug reactions

Corresponding authors: Hejian Zou, MD, Department of Rheumatology, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Central Urumqi Road, Shanghai, 200040, P.R. China, Phone: +86-21-52888048, E-mail: hejianzou@gmail.com; and Ming Guan, PhD, Department of Central Laboratory, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Central Urumqi Road, Shanghai, 200040, P.R. China, Phone: +86-21-52888048, Fax: +86-21-62481061, E-mail: guanming88@yahoo.com; and Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, P.R. China; and Department of Laboratory Medicine, North Huashan Hospital, Fudan University, Shanghai, P.R. China

aXinju Zhang and Huili Ma contributed equally to this study.

References

1. Kramer HM, Curhan G. The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988–1994. Am J Kidney Dis 2002;40:37–42.10.1053/ajkd.2002.33911Search in Google Scholar

2. Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012;64:1431–46.10.1002/acr.21772Search in Google Scholar

3. McInnes GT, Lawson DH, Jick H. Acute adverse reactions attributed to allopurinol in hospitalised patients. Ann Rheum Dis 1981;40:245–9.10.1136/ard.40.3.245Search in Google Scholar

4. Hoskison TK, Wortmann RL. Advances in the management of gout and hyperuricaemia. Scand J Rheumatol 2006;35:251–60.10.1080/03009740600855825Search in Google Scholar

5. Pluim HJ, van Deuren M, Wetzels JF. The allopurinol hypersensitivity syndrome. Neth J Med 1998;52:107–10.10.1016/S0300-2977(97)00088-0Search in Google Scholar

6. Kim SC, Newcomb C, Margolis D, Roy J, Hennessy S. Severe cutaneous reactions requiring hospitalization in allopurinol initiators: a population-based cohort study. Arthritis Care Res (Hoboken) 2013;65:578–84.10.1002/acr.21817Search in Google Scholar PubMed PubMed Central

7. Chia FL, Leong KP. Severe cutaneous adverse reactions to drugs. Curr Opin Allergy Clin Immunol 2007;7:304–9.10.1097/ACI.0b013e328216f54aSearch in Google Scholar PubMed

8. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994;331:1272–85.10.1056/NEJM199411103311906Search in Google Scholar PubMed

9. Gerull R, Nelle M, Schaible T. Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review. Crit Care Med 2011;39:1521–32.10.1097/CCM.0b013e31821201edSearch in Google Scholar PubMed

10. Pirmohamed M, Friedmann PS, Molokhia M, Loke YK, Smith C, Phillips E, et al. Phenotype standardization for immune-mediated drug-induced skin injury. Clin Pharmacol Ther 2011;89:896–901.10.1038/clpt.2011.79Search in Google Scholar PubMed

11. Dunckley H. HLA typing by SSO and SSP methods. Methods Mol Biol 2012;882:9–25.10.1007/978-1-61779-842-9_2Search in Google Scholar PubMed

12. Dalva K, Beksac M. Sequence-specific primed PCR (PCR-SSP) typing of HLA Class I and Class II alleles. Methods Mol Med 2007;134:51–60.10.1007/978-1-59745-223-6_4Search in Google Scholar PubMed

13. Dalva K, Beksac M. HLA typing with sequence-specific oligonucleotide primed PCR (PCR-SSO) and use of the Luminex technology. Methods Mol Med 2007;134:61–9.10.1007/978-1-59745-223-6_5Search in Google Scholar PubMed

14. Erlich H. HLA DNA typing: past, present, and future. Tissue Antigens 2012;80:1–11.10.1111/j.1399-0039.2012.01881.xSearch in Google Scholar PubMed

15. Kwok J, Kwong KM. Loop-mediated isothermal amplification for detection of HLA-B*58:01 allele. Tissue Antigens 2013;81:83–92.10.1111/tan.12042Search in Google Scholar PubMed

16. Notomi T, Okayama H, Masubuchi H, Yonekawa T, Watanabe K, Amino N, et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res 2000;28:E63.10.1093/nar/28.12.e63Search in Google Scholar PubMed PubMed Central

17. Mack SJ, Cano P, Hollenbach JA, He J, Hurley CK, Middleton D, et al. Common and well-documented HLA alleles: 2012 update to the CWD catalogue. Tissue Antigens 2013;81:194–203.10.1111/tan.12093Search in Google Scholar PubMed PubMed Central

18. Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA 2005;102:4134–9.10.1073/pnas.0409500102Search in Google Scholar PubMed PubMed Central

19. Kang HR, Jee YK, Kim YS, Lee CH, Jung JW, Kim SH, et al. Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics 2011;21:303–7.10.1097/FPC.0b013e32834282b8Search in Google Scholar PubMed

20. Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, et al. HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics 2008;9:1617–22.10.2217/14622416.9.11.1617Search in Google Scholar PubMed

21. Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S, et al. A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 2008;18:99–107.10.1097/FPC.0b013e3282f3ef9cSearch in Google Scholar PubMed

22. Cao ZH, Wei ZY, Zhu QY, Zhang JY, Yang L, Qin SY, 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;13:1193–201.10.2217/pgs.12.89Search in Google Scholar PubMed

23. Xu S, Yin X, Li S, Jin W, Lou H, Yang L, et al. Genomic dissection of population substructure of Han Chinese and its implication in association studies. Am J Hum Genet 2009;85:762–74.10.1016/j.ajhg.2009.10.015Search in Google Scholar PubMed PubMed Central

Received: 2014-3-7

Accepted: 2014-7-24

Published Online: 2014-9-26

Published in Print: 2015-2-1

You are currently not able to access this content.

Articles in the same Issue

https://doi.org/10.1515/cclm-2014-0251

Keywords for this article

allopurinol; HLA-B*58:01; severe cutaneous adverse drug reactions