Aim: To reveal the association of three class I HLA alleles, including HLA-A*33:03, HLA-B*58:01 and HLA-C*03:02, and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese patients. Methods: A case–control study on 100 allopurinol-induced SCARs patients, 183 tolerant controls and 810 population controls was performed. The HLA-A*33:03 and HLA-C*03:02 alleles were detected with the nested allele-specific PCR method; the HLA-B*58:01 allele was detected with the sequence-specific primer PCR method. Results: There were strong associations between HLA-B*58:01 and HLA-C*03:02 and allopurinol-induced SCARs. Specific associations were found between HLA-B*58:01 and Stevens–Johnson syndrome/toxic epidermal necrolysis and between HLA-C*03:02 and drug reaction with eosinophilia and systemic symptoms, with a gene dosage effect. The multivariate regression analysis indicated two significant independent risk factors: HLA-B*58:01/HLA-C*03:02 and estimated glomerular filtration rate <60 ml/min/1.73 m². The specificity, positive predictive value and negative predictive value of HLA-B*58:01 testing were higher than the HLA-C*03:02 or the multiplex testing, especially in patients with impaired renal function. Conclusion: The results supported pre-treatment HLA-B*58:01 testing in Vietnamese patients with declined renal function to prevent SCARs.

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References

1. Yang SC, Hu S, Zhang SZ et al. The epidemiology of Stevens–Johnson syndrome and toxic epidermal necrolysis in China. J. Immunol. Res. 2018, 4320195 (2018).
MedlineGoogle Scholar
2. Stamp LK, Chapman PT. Allopurinol hypersensitivity: pathogenesis and prevention. Best Pract. Res.: Clin. Rheumatol 34(4), 101501 (2020).
MedlineGoogle Scholar
3. Cho YT, Yang CW, Chu CY. Drug reaction with eosinophilia and systemic symptoms (DRESS): an interplay among drugs, viruses, and immune system. 18(6), 1243 (2017).
Google Scholar
4. Chung WH, Wang CW, Dao RL. Severe cutaneous adverse drug reactions. J. Dermatol. 43(7), 758–766 (2016).
Medline CASGoogle Scholar
5. Nguyen KD, Tran TN, Nguyen MT et al. Drug-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in Vietnamese spontaneous adverse drug reaction database: a subgroup approach to disproportionality analysis. J. Clin. Pharm. Ther. 44(1), 69–77 (2019).
Medline CASGoogle Scholar
6. Kang HR, Jee YK, Kim YS et al. Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet. Genomics 21(5), 303–307 (2011).
Medline CASGoogle Scholar
7. Stamp LK, Day RO, Yun J. Allopurinol hypersensitivity: investigating the cause and minimizing the risk. Nat. Rev. Rheumatol. 12(4), 235–242 (2016).
Medline CASGoogle Scholar
8. 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. USA 102(11), 4134–4139 (2005).
Medline CASGoogle Scholar
9. Wu X, Yang F, Chen S et al. Clinical, viral and genetic characteristics of drug reaction with eosinophilia and systemic symptoms (DRESS) in Shanghai, China. Acta Derm. Venereol. 98(4), 401–405 (2018).
Medline CASGoogle Scholar
10. Do MD, Mai TP, Do AD et al. Risk factors for cutaneous reactions to allopurinol in Kinh Vietnamese: results from a case–control study. Arthritis Res. Ther. 22(1), 182 (2020).
Medline CASGoogle Scholar
11. Nguyen DV, Chu HC, Vidal C et al. Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese. Pharmacogenomics 22(1), 1–12 (2021).
CASGoogle Scholar
12. Pham TTH, Tran QB, Sukasem C et al. A novel nested allele-specific PCR protocol for the detection of the HLA-A*33:03, a SCAR-associated allele, in Vietnamese people. Asian Pac. J. Allergy Immunol. doi:10.12932/AP-201120-1000 (2021) (Epub ahead of print).
Google Scholar
13. Pham TTH, Tran QB, Sukasem C et al. A novel allele-specific PCR protocol for the detection of the HLA-C*03:02 allele, a pharmacogenetic marker, in Vietnamese Kinh people. Appl. Clin. Genet. 14, 27–35 (2021).
Medline CASGoogle Scholar
14. Sassolas B, Haddad C, Mockenhaupt M et al. ALDEN, an algorithm for assessment of drug causality in Stevens–Johnson syndrome and toxic epidermal necrolysis: comparison with case–control analysis. Clin. Pharmacol. Ther. 88(1), 60–68 (2010).
Medline CASGoogle Scholar
15. Naranjo CA, Busto U, Sellers EM et al. A method for estimating the probability of adverse drug reactions. 30(2), 239–245 (1981).
Google Scholar
16. Roujeau JC. The spectrum of Stevens–Johnson syndrome and toxic epidermal necrolysis: a clinical classification. J. Invest. Dermatol. 102(6), S28–S30 (1994).
Medline CASGoogle Scholar
17. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann. Intern. Med. 130(6), 461–470 (1999).
Medline CASGoogle Scholar
18. Nguyen DV, Vida C, Chu HC, Fulton R, Li J, Fernando SL. Validation of a rapid, robust, inexpensive screening method for detecting the HLA-B*58:01 allele in the prevention of allopurinol-induced severe cutaneous adverse reactions. Allergy Asthma Immunol. Res. 9(1), 79–84 (2017).
Medline CASGoogle Scholar
19. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. 57(1), 289–300 (1995).
Google Scholar
20. Haldane JB. The estimation and significance of the logarithm of a ratio of frequencies. Ann. Hum. Genet. 20(4), 309–311 (1956).
Medline CASGoogle Scholar
21. Dormann CF, Elith J, Bacher S et al. Collinearity: a review of methods to deal with it and a simulation study evaluating their performance. 36(1), 27–46 (2013).
Google Scholar
22. Johnston R, Jones K, Manley D. Confounding and collinearity in regression analysis: a cautionary tale and an alternative procedure, illustrated by studies of British voting behaviour. Qual. Quant. 52(4), 1957–1976 (2018).
MedlineGoogle Scholar
23. Ko TM, Tsai CY, Chen SY et al. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ 351, h4848 (2015).
MedlineGoogle Scholar
24. Yu C, Mok C. Clinical Usefulness of HLA-B∗58:01 genotyping in gouty arthritis. J. Clin. Rheumatol. 19, 1–7 (2019).
Google Scholar
25. Yu KH, Yu CY, Fang YF. Diagnostic utility of HLA-B*5801 screening in severe allopurinol hypersensitivity syndrome: an updated systematic review and meta-analysis. Int. J. Rheum. Dis. 20(9), 1057–1071 (2017).
Medline CASGoogle Scholar
26. Li L, Zhang M, Holman DA. Population versus hospital controls for case–control studies on cancers in Chinese hospitals. BMC Med. Res. Methodol. 11(1), 167 (2011).
MedlineGoogle Scholar
27. Ruano-Ravina A, Pérez-Ríos M, Miguel Barros-Dios J. Population-based versus hospital-based controls: are they comparable? Gaceta Sanitaria 22(6), 609–613 (2008).
MedlineGoogle Scholar
28. Goncalo M, Coutinho I, Teixeira V et al. HLA-B*58:01 is a risk factor for allopurinol-induced DRESS and Stevens–Johnson syndrome/toxic epidermal necrolysis in a Portuguese population. Br. J. Dermatol. 169(3), 660–665 (2013).
Medline CASGoogle Scholar
29. Do MD, Le LGH, Nguyen VT et al. High-resolution HLA typing of HLA-A, -B, -C, -DRB1, and -DQB1 in Kinh Vietnamese by using next-generation sequencing. Front. Genet. 11, 383 (2020).
Medline CASGoogle Scholar
30. Hoa BK, Hang NT, Kashiwase K et al. HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in the Kinh population in Vietnam. Tissue Antigens 71(2), 127–134 (2008).
Medline CASGoogle Scholar
31. Ramasamy SN, Korb-Wells CS, Kannangara DRW et al. Allopurinol hypersensitivity: a systematic review of all published cases, 1950–2012. Drug Saf. 36(10), 953–980 (2013).
Medline CASGoogle Scholar
32. Wu R, Cheng YJ, Zhu LL et al. Impact of HLA-B* 58: 01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies. Oncotarget 7(49), 81870 (2016).
MedlineGoogle Scholar
33. Chung WH, Chang WC, Stocker SL et al. Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin. Ann. Rheum. Dis. 74(12), 2157–2164 (2015).
Medline CASGoogle Scholar
34. Ng CY, Yeh YT, Wang CW et al. Impact of the HLA-B(*) 58:01 allele and renal impairment on allopurinol-induced cutaneous adverse reactions. J. Invest. Dermatol. 136(7), 1373–1381 (2016).
Medline CASGoogle Scholar
35. Yun J, Mattsson J, Schnyder K et al. Allopurinol hypersensitivity is primarily mediated by dose-dependent oxypurinol-specific T cell response. Clin. Exp. Allergy 43(11), 1246–1255 (2013).
Medline CASGoogle Scholar
36. Plumpton CO, Alfirevic A, Pirmohamed M, Hughes DA. Cost effectiveness analysis of HLA-B*58:01 genotyping prior to initiation of allopurinol for gout. Rheumatology 56(10), 1729–1739 (2017).
Medline CASGoogle Scholar
37. Manson LEN, Swen JJ, Guchelaar HJ. Diagnostic test criteria for HLA genotyping to prevent drug hypersensitivity reactions: a systematic review of actionable HLA recommendations in CPIC and DPWG guidelines. Front Pharmacol. 11(1450), 1–8 (2020).
Google Scholar

Vol. 23, No. 5

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History

Received 14 December 2021

Accepted 31 January 2022

Published online 21 February 2022

Published in print April 2022

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Keywords

Author contributions

All authors contributed to the design of the study and edited the manuscript; TH Phung supervised the study and drafted the manuscript; TTH Pham performed the research and data analysis; CH Chu, DV Nguyen and HA Nguyen were responsible for recruitment of participants and SCAR evaluation; B TranQuang and TQN Do were responsible for genetic testing.

Financial & competing interests disclosure

This work was supported by grants from the Vietnam Ministry of Health, grant no. 4694/QD-BYT. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of the Vietnam National Institute of Hygiene and Epidemiology (IRB-VN01057-6/2018). Written informed consent was obtained from all subjects who were recruited.

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