| Title |
Genome-Wide Association and Replication Study of Hepatotoxicity Induced by Antiretrovirals Alone or with Concomitant Anti-Tuberculosis Drugs
|
|---|---|
| Published in |
OMICS: A Journal of Integrative Biology, April 2017
|
| DOI | 10.1089/omi.2017.0019 |
| Pubmed ID | |
| Authors |
Zelalem Petros, Ming Ta Michael Lee, Atsushi Takahashi, Yanfei Zhang, Getnet Yimer, Abiy Habtewold, Ina Schuppe-Koistinen, Taisei Mushiroda, Eyasu Makonnen, Michiaki Kubo, Eleni Aklillu |
| Abstract |
Drug-induced hepatotoxicity (DIH) is a common adverse event that is associated with both antiretroviral (ARV) and anti-tuberculosis drugs (ATD). Moreover, the genetic variations predisposing ARV- and ARV-ATD-induced liver toxicity in African populations are not well investigated, despite the two diseases being the major global health problems in sub-Saharan Africa. We performed a genome-wide association study (GWAS) and replication study to identify the genetic variants linked to the risk of developing DIH due to ARV drugs alone, and ARV-ATD co-treatment in Ethiopian HIV-positive patients. Treatment-naïve newly diagnosed HIV patients (n = 719) with or without tuberculosis (TB) co-infection were enrolled prospectively and received efavirenz-based ARV therapy with or without rifampicin-based short course ATD, respectively. Whole-genome genotyping was performed by using the Illumina Omni Express Exome Bead Chip genotyping array with 951,117 single nucleotide polymorphisms (SNPs) on a total of 41 cases of DIH, and 452 people without DIH (treatment tolerants). The replication study was carried out for 100 SNPs with the lowest p-values (top SNPs) by using an independent cohort consisting of 18 DIH cases and 208 treatment tolerants. We identified a missense SNP rs199650082 (2756G→A, R919Q, p = 1.4 × 10(-6), odds ratio [OR] = 18.2, 95% confidence interval [CI] = 7.1-46.9) in an endoplasmic reticulum to the nucleus signaling-1 (ERN1) gene on chromosome 17 to be associated with DIH in the ARV-only cohort. In the ARV-ATD co-treatment groups, rs4842407, a long intergenic noncoding RNAs (lincRNAs) transcript variant on chromosome 12, was associated with DIH (p = 5.3 × 10(-7), OR = 5.4, 95% CI = 2.8-10.3). These genetic variants that are putatively associated with DIH due to ARV drugs alone and ARV-ATD co-treatment establish a foundation for future personalized medicine in people with HIV and TB and call for larger studies in independent populations. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 65 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 65 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 11 | 17% |
| Student > Bachelor | 10 | 15% |
| Researcher | 10 | 15% |
| Student > Ph. D. Student | 6 | 9% |
| Student > Doctoral Student | 4 | 6% |
| Other | 7 | 11% |
| Unknown | 17 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 15 | 23% |
| Biochemistry, Genetics and Molecular Biology | 10 | 15% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 6% |
| Computer Science | 2 | 3% |
| Social Sciences | 2 | 3% |
| Other | 10 | 15% |
| Unknown | 22 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 April 2017.
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