Increased risk of strontium ranelate-related SJS/TEN is associated with HLA View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-08

AUTHORS

H. Y. Lee, M. X. Shen, Y. L. Lim, Y. K. Tay, M. M. F. Chan, S. M. Pang, Z. W. Xiao, S. B. Ang, E. C. Ren

ABSTRACT

Severe adverse drug reactions (ADR) of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in some patients receiving strontium ranelate have been reported, but the risk factors are unclear. We show that HLA-A*33:03 and B*58:01 are significantly associated with patients who developed SJS/TEN; and provide the first evidence that genetic risk factors are involved in strontium ranelate-associated SJS/TEN. INTRODUCTION: In this study, HLA as a genetic risk factor was assessed among osteoporotic patients prescribed with strontium ranelate that developed severe cutaneous adverse drug reactions (SCARs) compared with those who were tolerant. METHODS: Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) of patients was HLA typed using sequencing-based typing method to determine their HLA profiles. RESULTS: Osteoporotic patients who are currently on strontium ranelate were enrolled in the study (n = 76). Tolerant controls were defined as patients who received strontium ranelate for a minimum of 3 months (range 3 months to 8 years) with no reports of any cutaneous reactions as these reactions usually occur within the first 12 weeks after starting treatment. Retrospective cases of SJS/TEN were also identified (n = 5). The majority of the accrued samples were of Han Chinese descent: controls (n = 72) and cases (n = 4). All cases and controls were genotyped at four HLA genes, namely HLA-A, HLA-B, HLA-C, and HLA-DRB1. In comparing the samples of Han Chinese descent (72 controls and 4 cases), we found significant associations with HLA-A*33:03 (p = 0.002) and HLA-B*58:01 (p = 0.023). There was no significant association with any HLA-C or HLA-DRB1 alleles. CONCLUSIONS: This study reveals that the occurrence of SJS/TEN in Han Chinese patients receiving strontium ranelate is HLA associated. This has important clinical implications for understanding the underlying mechanisms for this ADR as well as evaluating the potential role of genetic pre-screening for osteoporotic patients who may be prescribed strontium ranelate. More... »

PAGES

2577-2583

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00198-016-3568-9

DOI

http://dx.doi.org/10.1007/s00198-016-3568-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000527012

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27003892


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    "description": "Severe adverse drug reactions (ADR) of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in some patients receiving strontium ranelate have been reported, but the risk factors are unclear. We show that HLA-A*33:03 and B*58:01 are significantly associated with patients who developed SJS/TEN; and provide the first evidence that genetic risk factors are involved in strontium ranelate-associated SJS/TEN.\nINTRODUCTION: In this study, HLA as a genetic risk factor was assessed among osteoporotic patients prescribed with strontium ranelate that developed severe cutaneous adverse drug reactions (SCARs) compared with those who were tolerant.\nMETHODS: Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) of patients was HLA typed using sequencing-based typing method to determine their HLA profiles.\nRESULTS: Osteoporotic patients who are currently on strontium ranelate were enrolled in the study (n\u2009=\u200976). Tolerant controls were defined as patients who received strontium ranelate for a minimum of 3\u00a0months (range 3\u00a0months to 8\u00a0years) with no reports of any cutaneous reactions as these reactions usually occur within the first 12\u00a0weeks after starting treatment. Retrospective cases of SJS/TEN were also identified (n\u2009=\u20095). The majority of the accrued samples were of Han Chinese descent: controls (n\u2009=\u200972) and cases (n\u2009=\u20094). All cases and controls were genotyped at four HLA genes, namely HLA-A, HLA-B, HLA-C, and HLA-DRB1. In comparing the samples of Han Chinese descent (72 controls and 4 cases), we found significant associations with HLA-A*33:03 (p\u2009=\u20090.002) and HLA-B*58:01 (p\u2009=\u20090.023). There was no significant association with any HLA-C or HLA-DRB1 alleles.\nCONCLUSIONS: This study reveals that the occurrence of SJS/TEN in Han Chinese patients receiving strontium ranelate is HLA associated. This has important clinical implications for understanding the underlying mechanisms for this ADR as well as evaluating the potential role of genetic pre-screening for osteoporotic patients who may be prescribed strontium ranelate.", 
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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00198-016-3568-9'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00198-016-3568-9'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00198-016-3568-9'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00198-016-3568-9'


 

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