HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Nicoletti, PaolaWerk, Anneke N
Sawle, Ashley
Shen, Yufeng
Urban, Thomas J
Coulthard, Sally A
Bjornsson, Einar S
Cascorbi, Ingolf
Floratos, Aris
Stammschulte, Thomas
Gundert-Remy, Ursula
Nelson, Matthew R
Aithal, Guruprasad P
Daly, Ann K
Issue Date
2016-05
Metadata
Show full item recordCitation
HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury. 2016, 26 (5):218-24 Pharmacogenet. GenomicsAbstract
Flupirtine is a nonopioid analgesic with regulatory approval in a number of European countries. Because of the risk of serious liver injury, its use is now limited to short-term pain management. We aimed to identify genetic risk factors for flupirtine-related drug-induced liver injury (DILI) as these are unknown.Six flupirtine-related DILI patients from Germany were included in a genome-wide association study (GWAS) involving a further 614 European cases of DILI because of other drugs and 10 588 population controls. DILI was diagnosed by causality assessment and expert review. Human leucocyte antigen (HLA) and single nucleotide polymorphism genotypes were imputed from the GWAS data, with direct HLA typing performed on selected cases to validate HLA predictions. Four replication cases that were unavailable for the GWAS were genotyped by direct HLA typing, yielding an overall total of 10 flupirtine DILI cases.
In the six flupirtine DILI cases included in the GWAS, we found a significant enrichment of the DRB1*16:01-DQB1*05:02 haplotype compared with the controls (minor allele frequency cases 0.25 and minor allele frequency controls 0.013; P=1.4×10). We estimated an odds ratio for haplotype carriers of 18.7 (95% confidence interval 2.5-140.5, P=0.002) using population-specific HLA control data. The result was replicated in four additional cases, also with a haplotype frequency of 0.25. In the combined cohort (six GWAS plus four replication cases), the haplotype was also significant (odds ratio 18.7, 95% confidence interval 4.31-81.42, P=6.7×10).
We identified a novel HLA class II association for DILI, confirming the important contribution of HLA genotype towards the risk of DILI generally.
Description
To access publisher's full text version of this article click on the hyperlink at the bottom of the pageAdditional Links
http://dx.doi.org/ 10.1097/FPC.0000000000000209Rights
Archived with thanks to Pharmacogenetics and genomicsae974a485f413a2113503eed53cd6c53
10.1097/FPC.0000000000000209
Scopus Count
Collections
Related articles
- Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles.
- Authors: Lucena MI, Molokhia M, Shen Y, Urban TJ, Aithal GP, Andrade RJ, Day CP, Ruiz-Cabello F, Donaldson PT, Stephens C, Pirmohamed M, Romero-Gomez M, Navarro JM, Fontana RJ, Miller M, Groome M, Bondon-Guitton E, Conforti A, Stricker BH, Carvajal A, Ibanez L, Yue QY, Eichelbaum M, Floratos A, Pe'er I, Daly MJ, Goldstein DB, Dillon JF, Nelson MR, Watkins PB, Daly AK, Spanish DILI Registry., EUDRAGENE., DILIN., DILIGEN., International SAEC.
- Issue date: 2011 Jul
- A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury.
- Authors: Cirulli ET, Nicoletti P, Abramson K, Andrade RJ, Bjornsson ES, Chalasani N, Fontana RJ, Hallberg P, Li YJ, Lucena MI, Long N, Molokhia M, Nelson MR, Odin JA, Pirmohamed M, Rafnar T, Serrano J, Stefánsson K, Stolz A, Daly AK, Aithal GP, Watkins PB, Drug-Induced Liver Injury Network (DILIN) investigators., International DILI consortium (iDILIC).
- Issue date: 2019 May
- Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study.
- Authors: Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M, Barnhart HX, Bondon-Guitton E, Hayashi PH, Bessone F, Carvajal A, Cascorbi I, Cirulli ET, Chalasani N, Conforti A, Coulthard SA, Daly MJ, Day CP, Dillon JF, Fontana RJ, Grove JI, Hallberg P, Hernández N, Ibáñez L, Kullak-Ublick GA, Laitinen T, Larrey D, Lucena MI, Maitland-van der Zee AH, Martin JH, Molokhia M, Pirmohamed M, Powell EE, Qin S, Serrano J, Stephens C, Stolz A, Wadelius M, Watkins PB, Floratos A, Shen Y, Nelson MR, Urban TJ, Daly AK, International Drug-Induced Liver Injury Consortium, Drug-Induced Liver Injury Network Investigators, and International Serious Adverse Events Consortium.
- Issue date: 2017 Apr
- Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury.
- Authors: Donaldson PT, Daly AK, Henderson J, Graham J, Pirmohamed M, Bernal W, Day CP, Aithal GP
- Issue date: 2010 Dec
- The association of HLA-DRB1 and HLA-DQB1 alleles with genetic susceptibility to multiple sclerosis in the Slovak population.
- Authors: Michalik J, Čierny D, Kantorová E, Kantárová D, Juraj J, Párnická Z, Kurča E, Dobrota D, Lehotský J
- Issue date: 2015