# The Impact of Organic Anion-Transporting Polypeptide (OATP) Variants on the Side Effects of Direct-Acting Antivirals in Hepatitis C Patients

**Authors:** Zuhal Altintas, Engin Altintas

PMC · DOI: 10.7759/cureus.82213 · Cureus · 2025-04-13

## TL;DR

This study found that a specific genetic variant in OATP1B3 is linked to side effects from hepatitis C treatments called direct-acting antivirals.

## Contribution

The study identifies a novel association between the OATP1B3 c.334T>G variant and DAA-related side effects in hepatitis C patients.

## Key findings

- The OATP1B3 c.334T>G variant was significantly associated with treatment-related side effects (p = 0.030).
- Haplotype ratios of OATP1B1 c.388A>G and c.521T>C differed significantly between patients and controls (p = 0.036).

## Abstract

Background

Organic anion-transporting polypeptides (OATPs) are responsible for the cellular uptake of a broad range of endogenous compounds and xenobiotics in multiple tissues. The aim of our study was to determine whether variations in OATP1B1 and OATP1B3 affect the side effects experienced by hepatitis C patients treated with direct-acting antivirals (DAAs).

Methods

This study included 199 hepatitis C patients treated with DAAs. Ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir ± dasabuvir and 162 control individuals without hepatitis C. Treatment-related side effects were recorded. The OATP1B1 gene variations c.388A>G and c.521T>C and the OATP1B3 gene variations c.334T>G and c.699G>A were analyzed via the polymerase chain reaction-restriction fragment length polymorphism method. Allele/genotype combinations of OATP1B1 and OATP1B3 haplotypes were evaluated.

Results

Side effects were observed in 53 (26.6%) of 199 hepatitis C patients. There were skin mucosal lesions in 19 patients (36%), fatigue in 18 patients (34%), pruritus in 11 patients (20.5%), and other in five patients (9.5%). There was a significant relationship between the c.334T>G variant and side effects (p = 0.030). The frequency distribution of the c.334T>G variant was in Hardy-Weinberg equilibrium. The frequencies of the patient group and the control group were 65.3% and 63%, respectively. We found a significant difference between the patient and control groups in terms of the haplotype ratios of c.388A>G and c.521T>C (p = 0.036).

Conclusions

We found a significant relationship between the c.334T>G variant in OATP1B3 and DAA-related side effects in hepatitis C patients.

## Linked entities

- **Genes:** SLCO1B1 (solute carrier organic anion transporter family member 1B1) [NCBI Gene 10599], SLCO1B3 (solute carrier organic anion transporter family member 1B3) [NCBI Gene 28234]
- **Chemicals:** ledipasvir (PubChem CID 67505836), sofosbuvir (PubChem CID 45375808), ombitasvir (PubChem CID 54767916), paritaprevir (PubChem CID 45110509), ritonavir (PubChem CID 5076), dasabuvir (PubChem CID 56640146)

## Full-text entities

- **Genes:** SLCO2B1 (solute carrier organic anion transporter family member 2B1) [NCBI Gene 11309] {aka OATP-B, OATP2B1, OATPB, SLC21A9}, CYP2C19 (cytochrome P450 family 2 subfamily C member 19) [NCBI Gene 1557] {aka CPCJ, CYP2C, CYPIIC17, CYPIIC19, P450C2C, P450IIC19}, SLCO1A2 (solute carrier organic anion transporter family member 1A2) [NCBI Gene 6579] {aka OATP, OATP-A, OATP1A2, SLC21A3}, CYP3A4 (cytochrome P450 family 3 subfamily A member 4) [NCBI Gene 1576] {aka CP33, CP34, CYP3A, CYP3A3, CYPIIIA3, CYPIIIA4}, NS2 [NCBI Gene 57762], CYP2C9 (cytochrome P450 family 2 subfamily C member 9) [NCBI Gene 1559] {aka CPC9, CYP2C, CYP2C10, CYPIIC9, P450-2C9, P450IIC9}, SLCO1B1 (solute carrier organic anion transporter family member 1B1) [NCBI Gene 10599] {aka HBLRR, LST-1, OATP-C, OATP1B1, OATP2, OATPC}, UGT1A1 (UDP glucuronosyltransferase family 1 member A1) [NCBI Gene 54658] {aka BILIQTL1, GNT1, HUG-BR1, UDPGT, UDPGT 1-1, UGT1}, CYP2D6 (cytochrome P450 family 2 subfamily D member 6 (gene/pseudogene)) [NCBI Gene 1565] {aka CPD6, CYP2D, CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2}, SLCO1B3 (solute carrier organic anion transporter family member 1B3) [NCBI Gene 28234] {aka HBLRR, LST-2, LST-3TM13, LST3, OATP-8, OATP1B3}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}
- **Diseases:** loss of appetite (MESH:D001068), chronic liver disease (MESH:D008107), cracked tongue (MESH:D003387), tremors (MESH:D014202), proteinuria (MESH:D011507), myopathy (MESH:D009135), sores inside the mouth (MESH:D009059), skin rash (MESH:D005076), toxicity (MESH:D064420), HCV (MESH:D006526), irritability (MESH:D001523), dry mouth (MESH:D014987), dyspnea (MESH:D004417), headache (MESH:D006261), itching (MESH:D011537), anemia (MESH:D000740), sweating (MESH:D013543), hot flashes (MESH:D019584), fatigue (MESH:D005221), vision loss (MESH:D014786), blistering of the skin (MESH:D001768), hair loss (MESH:D000505), cough (MESH:D003371), rhabdomyolysis (MESH:D012206), Rotor syndrome (MESH:D006933), Skin lesions (MESH:D012871), arthralgia (MESH:D018771), hyperbilirubinemia (MESH:D006932), diarrhea (MESH:D003967), hepatocellular carcinomas (MESH:D006528), cancer (MESH:D009369), depression (MESH:D003866), oropharyngeal pain (MESH:D009959), nausea (MESH:D009325), cirrhosis (MESH:D005355), liver cirrhosis (MESH:D008103), autosomal recessive disease (MESH:D030342), Hepatitis C (MESH:D019698)
- **Chemicals:** lipid (MESH:D008055), glibenclamide (MESH:D005905), ATP (MESH:D000255), ledipasvir (MESH:C586541), dioscin (MESH:C019357), repaglinide (MESH:C072379), paclitaxel (MESH:D017239), fluvastatin (MESH:D000077340), atorvastatin (MESH:D000069059), DSV (-), atazanavir (MESH:D000069446), cyclosporin A (MESH:D016572), epigallocatechin gallate (MESH:C045651), pravastatin (MESH:D017035), fexofenadine (MESH:C093230), taurocholate (MESH:D013656), EDTA (MESH:D004492), simeprevir (MESH:D000069616), coproporphyrins (MESH:D003306), dasabuvir (MESH:C588260), atrasentan (MESH:D000077868), velpatasvir (MESH:C000604171), sodium (MESH:D012964), indocyanine green (MESH:D007208), testosterone (MESH:D013739), simvastatin acid (MESH:C063287), glipizide (MESH:D005913), imatinib (MESH:D000068877), docetaxel (MESH:D000077143), CCK-8 (MESH:D012844), RTV (MESH:D019438), SOF (MESH:D000069474), simvastatin (MESH:D019821), thyroxine (MESH:D013974), triiodothyronine (MESH:D014284), bilirubin (MESH:D001663), bile salts (MESH:D001647), ouabain (MESH:D010042), methotrexate (MESH:D008727), gemfibrozil (MESH:D015248), telaprevir (MESH:C486464), RBV (MESH:D012254), epicatechin gallate (MESH:C062669), rifampicin (MESH:D012293), boceprevir (MESH:C512204), LS (MESH:C000595958), digoxin (MESH:D004077)
- **Species:** Homo sapiens (human, species) [taxon 9606], hepatitis C virus [taxon 11103], Human immunodeficiency virus 1 (no rank) [taxon 11676]
- **Mutations:** 388GG, 334TG, C1007G, 521C, 699GG, rs4149056

## Full text

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## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12075992/full.md

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Source: https://tomesphere.com/paper/PMC12075992