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This study investigated variation in NR1I2 and NR1I3 and its effect on plasma efavirenz levels in HIV/AIDS patients. Variability in plasma drug levels has largely led research on identifying causative variants in drug metabolising enzyme (DME) genes, with little focus on the nuclear receptor genes NR1I2 and NR1I3, coding for PXR and CAR, respectively, that are involved in regulating DMEs.
Methods464 Bantu-speaking South Africans comprising of HIV/AIDS patients on efavirenz-based treatment (n=301) and 163 healthy subjects were genotyped for 6 SNPs in NR1I2 and NR1I3. 32 of the 301 patients had their DNA binding domains (DBDs) in NR1I2 and NR1I3 sequenced.
ResultsSignificantly decreased efavirenz plasma concentrations were observed in patients carrying the NR1I3 rs3003596C/C and T/C genotypes (P=0.015 and P=0.010, respectively). Sequencing resulted in the discovery of a further 13 SNPs, 3 of which are novel variants in the DBD of NR1I2. There were significant differences in the distribution of NR1I2 and NR1I3 SNPs between South Africans when compared to Caucasian, Asian and Yoruba population groups.
ConclusionFor the realisation of personalised medicine, PXR and CAR genetic variation should be taken into consideration because of their involvement in the regulation of DMEs.
相似文献Oborna I, Malickova K, Fingerova H, Brezinova J, Horka P, Novotny J, Bryndova H, Filipcikova R, Svobodova M. A Randomized controlled trial of lycopene treatment on soluble receptor for advanced glycation end products in seminal and blood plasma of normospermic men. Am J Reprod Immunol 2011; 66: 179–184 Problem The aim of present study was to investigate the effects of antioxidant lycopene on soluble receptor for advanced glycation end products (sRAGE) levels in blood and seminal plasma in normospermic males. Methods Study included 15 fertile volunteers and 13 normospermic male partners from infertile relationships. The treatment was 12‐week administration of 20 mg of lycopene or placebo followed by crossover and treatment for a further 12 weeks. The ELISA kit Quantikine® was used to determine sRAGE levels. Results Lycopene administration decreased sRAGE levels in seminal plasma in fertile volunteers (controls) as well as in male partners in the infertile relationships group (P = 0.008 and P = 0.012, respectively). No significant effect of lycopene on sRAGE in blood plasma was found in either group, but seminal plasma sRAGE was significantly suppressed. Conclusion Lycopene decreased sRAGE in seminal, but not in blood plasma. This may be because of selective local uptake of lycopene in the male reproductive tract, namely in prostate. Decreased sRAGE may be caused by lycopene suppression of oxidative stressors and explain in part the putative improvement in fertility reported after lycopene treatment. 相似文献