Publication: Genome-wide association study identifies variations in 6p21.3 associated with nevirapine-induced rash
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Issued Date
2011
Resource Type
File Type
application/pdf
ISSN
10584838
Other identifier(s)
2-s2.0-79961219567
Rights Holder(s)
มหาวิทยาลัยศรีนครินทรวิโรฒ
Bibliographic Citation
Clinical Infectious Diseases. Vol 53, No.4 (2011), p.341-348
Suggested Citation
Chantarangsu S., Mushiroda T., Mahasirimongkol S., Kiertiburanakul S., Sungkanuparph S., Manosuthi W., Tantisiriwat W., Charoenyingwattana A., Sura T., Takahashi A., Kubo M., Kamatani N., Chantratita W., Nakamura Y. Genome-wide association study identifies variations in 6p21.3 associated with nevirapine-induced rash. Clinical Infectious Diseases. Vol 53, No.4 (2011), p.341-348. doi:10.1093/cid/cir403 Retrieved from: https://hdl.handle.net/20.500.14740/7265
Abstract
Background. We aimed to identify disease-predisposing variations with nevirapine-induced rash using genome-wide single-nucleotide polymorphisms (SNPs) as genetic markers. Methods. A genome-wide association study (GWAS) was performed using-550000 markers in 72 human immunodeficiency virus (HIV)-infected Thai patients with nevirapine-induced rash and 77 nevirapine-tolerant patients, and then candidate SNPs were further evaluated in a replication set (88 patients with nevirapine-induced rash and 145 nevirapine-tolerant patients). Results. The genome-wide association analysis and replication studies of candidate SNPs identified significant associations of nevirapine-induced rash with 2 SNPs (rs1265112 and rs746647) within CCHCR1 on chromosome 6p21.3 (P GWAS = 1.6 × 10 -4; P replication = 2.6 × 10 -5; P combined = 1.2 × 10 -8). The odds ratio (OR) of the risk genotypes under a dominant model was 4.36 (95% confidence interval [CI], 2.58-7.36). The noncoding SNPs rs1265112 and rs746647 were in complete linkage disequilibrium with the nonsynonymous SNP rs1576 (r 2 5 1.00), which has been associated with psoriasis. The logistic regression analysis also indicated genetic variations in CCHCR1 to be significantly associated with rash, with an OR of 2.59 (95% CI, 1.82-3.68; P = .007). The receiver operating characteristic curve showed that the algorithm had an area under the curve of 76.4%, which was developed with 5 factors: rs1576*G status, HLA-B*3505 status, not receiving prescribed lead-in of nevirapine, history of drug allergy, and CD4 cell count prior to the nevirapine treatment. Conclusions. We demonstrated that genetic variations in CCHCR1 are strongly associated with nevirapineinduced rash. A predictive model that includes genetic and clinical risk factors for nevirapine-associated rash might be useful in lowering the incidence of rash associated with nevirapine initiation among HIV-infected patients. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Subject(s)
Coiled coil alpha helical rod protein1
Nevirapine
Peptides and proteins
Unclassified drug
Case control study
CD4 lymphocyte count
Chromosome 6p
Controlled study
Disease predisposition
Disease severity
Drug eruption
Drug hypersensitivity
Drug tolerance
Genetic association
Genetic variability
Human
Human immunodeficiency virus infected patient
Human immunodeficiency virus infection
Major clinical study
Medical history
Nucleotide sequence
Priority journal
Psoriasis
Retrospective study
Review
Single nucleotide polymorphism
Thailand
Anti-HIV Agents
Chromosomes, Human, Pair 6
Drug Eruptions
Genetic Predisposition to Disease
Genome-Wide Association Study
HIV Infections
Humans
Intracellular Signaling Peptides and Proteins
Lamivudine
Logistic Models
Nevirapine
Polymorphism, Single Nucleotide
Retrospective Studies
Risk Factors
ROC Curve
Stavudine
Thailand
Nevirapine
Peptides and proteins
Unclassified drug
Case control study
CD4 lymphocyte count
Chromosome 6p
Controlled study
Disease predisposition
Disease severity
Drug eruption
Drug hypersensitivity
Drug tolerance
Genetic association
Genetic variability
Human
Human immunodeficiency virus infected patient
Human immunodeficiency virus infection
Major clinical study
Medical history
Nucleotide sequence
Priority journal
Psoriasis
Retrospective study
Review
Single nucleotide polymorphism
Thailand
Anti-HIV Agents
Chromosomes, Human, Pair 6
Drug Eruptions
Genetic Predisposition to Disease
Genome-Wide Association Study
HIV Infections
Humans
Intracellular Signaling Peptides and Proteins
Lamivudine
Logistic Models
Nevirapine
Polymorphism, Single Nucleotide
Retrospective Studies
Risk Factors
ROC Curve
Stavudine
Thailand