ABSTRACT
Pulsed low-dose cyclophosphamide (CTX) therapy has become a very effective approach in improving the clinical outcomes of lupus nephritis (LN) patients. However, variations of CTX therapeutic outcomes in LN patients are incompletely understood. We investigated the contributions of known allelic variants to CTX therapy outcomes in 77 LN patients. Then, 22 out of the 77 patients were randomly enrolled to evaluate the pharmacokinetic profiles. LN patients with a GSTA1*A mutation (CT heterozygous) had more risk of non-remission (44% vs. 20%, P=0.005). Pharmacokinetic data indicated that patients with a GSTA1*A heterozygous variant had a lower exposure to 4-hydroxycyclophosphamide (4OHCTX) compared to wild-type patients (AUC4OHCTX: 12.8 (9.8, 19.5) vs. 27.5 (18.1, 32.8) h mg/l, P=0.023). Clinical remission was significantly related to higher exposure of 4OHCTX (P=0.038). In conclusion, LN patients with GSTA1*A heterozygous genotypes had poor CTX treatment remission due to less exposure to activated metabolites of CTX.
Subject(s)
Cyclophosphamide/therapeutic use , Glutathione Transferase/genetics , Immunosuppressive Agents/therapeutic use , Lupus Nephritis/drug therapy , Adult , Aged , Cyclophosphamide/analogs & derivatives , Cyclophosphamide/metabolism , Cyclophosphamide/pharmacokinetics , Female , Glutathione Transferase/metabolism , Heterozygote , Humans , Immunosuppressive Agents/pharmacokinetics , Lupus Nephritis/genetics , Male , Middle Aged , Pharmacogenetics , Polymorphism, Genetic , Remission Induction , Treatment Outcome , Young AdultABSTRACT
The cigarette beetle, Lasioderma serricorne (Fabricius), is an important pest of stored commodities and distributed widely in the world. Here, we report the complete mitochondrial genome of L. serricorne which was 15,958 bp and composed of 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and a control region. The gene order and orientation of L. serricorne were identical to those of other Coleopteran mitogenomes. ATG, ATA, ATT, ATC, TTG were initiation codons and TAA, TAG, T were termination codons. All 22 tRNA genes were predicted with a typical cloverleaf structure except for trnS1 (AGN). Phylogenetic analysis performed using 13 PCGs with 14 other beetles showed that L. serricorne is closely related to Stegobium paniceum, which agree with the conventional taxonomy.