Genetic polymorphisms in drug metabolism and transport genes can influence the pharmacokinetics and pharmacodynamics of chemotherapy drugs. We investigated the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. The association between the eight polymorphisms with response to chemotherapy and clinical outcome of patients was carried out by unconditional logistic regression analysis and Cox proportional hazard models. Of 186 patients, 98 patients showed good response to chemotherapy, 64 died, and 97 showed progression at the end of the study. Patients carrying ABCB1 rs1128503 TT genotype and T allele were more likely to have a good response to chemotherapy. ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were associated with poor response to chemotherapy. In the Cox proportional hazards model, after adjusting for potential confounding factors, patients carrying ABCB1 rs1128503 TT genotype and T allele were associated with lower risk of progression-free survival (PFS) and overall survival (OS). ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were correlated with high risk of PFS and OS. The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter OS. In conclusion, variants of ABCB1 rs128503, ABCC3 rs4148416, and GSTP1 rs1695 are associated with response to chemotherapy and PFS and OS of osteosarcoma patients; these gene polymorphisms could help in the design of individualized therapy.
ObJEctIVE: Osteoporosis is a serious and common health issue of considerable complexity among postmenopausal women. the osteoprotegerin gene (OPG) is considered to play an important role in the pathogenesis of osteoporosis. the objective of this study was to detect single nucleotide polymorphisms (sNPs) in the OPG gene and assess the association between bone mineral density (bMD) and sNPs in postmenopausal women. MEtHODs: bMD was measured at the lumbar spine (L2-4), neck, and total hip by dual energy X-ray absorptiometry (DEXA). the polymerase chain reaction-restriction fragment length polymorphism (PcrrFLP), created restriction site-Pcr (crs-Pcr), and DNA sequencing methods were used to identify the g.19163A>G and g.23298t>c polymorphisms and genotypes in 739 chinese postmenopausal women. rEsULts: Our data suggest that g.19163A>G was significantly associated with adjusted spine bMD, neck hip bMD, and total hip bMD. subjects with genotype AA had significantly higher bMD value than those of genotypes AG and GG (P <0.05). We failed to detect any statistically significant association between g.23298t>c and adjusted spine bMD and neck hip bMD, while it almost reached a significant association with the adjusted total hip bMD (P = 0.058). DIscUssION: these findings indicate that the OPG gene is related to bMD and osteoporosis in chinese postmenopausal women.
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