International journal of clinical pharmacology and therapeutics · 2019
11β-hydroxysteroid dehydrogenase type 1 is associated with antiretroviral therapy-induced increase in low-density lipoprotein cholesterol .
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Niki Kazuyuki, Harada Kazuo, Hikasa Shinich, Tsugane Mamiko, Ueda Mikiko, Higasa Satoshi, Kimura Takeshi, Takagi Tatsuya, Uejima Etsuko
Аннотация
OBJECTIVE: To investigate the association between 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity and antiretroviral therapy (ART)-induced increase in low-density lipoprotein cholesterol (LDL).
MATERIALS AND METHODS: We enrolled 62 patients and used liquid chromatography-tandem mass spectrometry to measure 11β-HSD1 activity, which was expressed as a ratio of the sum of urinary tetrahydrocortisol and allo-tetrahydrocortisol concentrations to urinary tetrahydrocortisone concentration. Patient data, including baseline laboratory values, were extracted from medical records for logistic regression analyses of factors associated with LDL increase during ART. The cutoff 11β-HSD1 activity ratio associated with the LDL increase during ART was determined using receiver operator characteristic (ROC) curve analysis.
RESULTS: The LDL level increased significantly from 88.8 mg/dL before ART to 106.7 mg/dL during ART (p = 0.04). Additionally, patients with increased LDL tended to have a higher 11β-HSD1 activity ratio (1.59 vs. 1.21, p = 0.06) and longer duration of ART (13.9 vs. 10.2 months, p = 0.07) than patients with unchanged or decreased LDL. The cutoff 11β-HSD1 activity ratio was 1.226. Results of the univariate logistic regression analysis suggested that 11β-HSD1 activity ratio ≥ 1.226 was associated with LDL increase during ART (p = 0.011), with an odds ratio of 8.000.
CONCLUSION: This study revealed the possible association between 11β-HSD1 activity and ART-induced LDL increase. The findings of this study suggest that 11β-HSD1 could be a useful drug target for the treatment of ART-induced hyperlipidemia.
MATERIALS AND METHODS: We enrolled 62 patients and used liquid chromatography-tandem mass spectrometry to measure 11β-HSD1 activity, which was expressed as a ratio of the sum of urinary tetrahydrocortisol and allo-tetrahydrocortisol concentrations to urinary tetrahydrocortisone concentration. Patient data, including baseline laboratory values, were extracted from medical records for logistic regression analyses of factors associated with LDL increase during ART. The cutoff 11β-HSD1 activity ratio associated with the LDL increase during ART was determined using receiver operator characteristic (ROC) curve analysis.
RESULTS: The LDL level increased significantly from 88.8 mg/dL before ART to 106.7 mg/dL during ART (p = 0.04). Additionally, patients with increased LDL tended to have a higher 11β-HSD1 activity ratio (1.59 vs. 1.21, p = 0.06) and longer duration of ART (13.9 vs. 10.2 months, p = 0.07) than patients with unchanged or decreased LDL. The cutoff 11β-HSD1 activity ratio was 1.226. Results of the univariate logistic regression analysis suggested that 11β-HSD1 activity ratio ≥ 1.226 was associated with LDL increase during ART (p = 0.011), with an odds ratio of 8.000.
CONCLUSION: This study revealed the possible association between 11β-HSD1 activity and ART-induced LDL increase. The findings of this study suggest that 11β-HSD1 could be a useful drug target for the treatment of ART-induced hyperlipidemia.