The Analysis of
            <i>DKK1</i>
            Polymorphisms in Relation to Skeletal Phenotypes and Bone Response to Alendronate Treatment in Chinese Postmenopausal Women

Wang, Jianyi; Zhou, Peiran; Liu, Yi; Xu, Xiaowei; Ma, Dongjie; Xia, Weibo; Jiang, Yan; Wang, Ou; Xing, Xiaoping; Li, Mei

doi:10.2217/pgs.15.167

Cited by 7 publications

(3 citation statements)

References 34 publications

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“…However, as we observed in clinic, the efficacy and safety of bisphosphonate were variable. Previous studies reported that the associations between treatment response to alendronate and genetic variants in the candidate gene of the mevalonate pathway 10, the OPG/RANKL/RANK signaling pathway [ 28 ] and the Wnt/β-catenin signaling pathway [ 29 , 30 , 31 ], indicate that interpatient variability could be due to inherited interindividual differences. However, genetic pharmacological studies about bone response to zoledronic treatment are very limited.…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms of Nuclear Factor-κB Family Affect the Bone Mineral Density Response to Zoledronic Acid Therapy in Postmenopausal Chinese Women

Wang

et al. 2022

Genes

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The aim of this study was to explore the allelic association between genetic polymorphisms of the NF-κB pathway and the variance of clinical effects of zoledronic in postmenopausal Chinese women with osteoporosis. In the study, 110 Chinese postmenopausal women with osteoporosis were recruited. Every patient received zoledronic once a year. BMD was measured at baseline and after one year of treatment. The 13 tagger SNPs of five genes in the NF-κB pathway were genotyped. In the study, 101 subjects completed the one-year follow-up. The ITCTG and DTCTG haplotypes, which are constituted of rs28362491, rs3774937, rs230521, rs230510 and rs4648068 of the NF-κB1 gene, were associated with improvement in BMD at L1-4 and femoral neck (p < 0.001, p = 0.008, respectively). The CGC haplotype, which is constituted of rs7119750, rs2306365 and rs11820062 of the RELA gene, was associated with improvement in BMD at total hip (p < 0.001). After Bonferroni correction, haplotypes ITCTG and CGC still showed significant association with the % change of BMD at L1-4 and total hip. Therefore, NF-κB1 and RELA gene were significantly associated with bone response to the treatment of zoledronic in postmenopausal Chinese women with osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms of Nuclear Factor-κB Family Affect the Bone Mineral Density Response to Zoledronic Acid Therapy in Postmenopausal Chinese Women

Wang

et al. 2022

Genes

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“…77 Many researchers focused on the complex associations between mutations in Wnt pathway genes and bladder cancer, such as secreted frizzled-related protein 1 rs3242. 78 Wang JY et al 79 discovered that Dkk1 rs2241529 correlated to baseline BMD. As emerging molecular biomarkers, some variants of Wnt siganaling pathway genes are in the process of translation to the clinic to help clinical diagnosis and treatment.…”

Section: Wnt Signaling and Diagnosticsmentioning

confidence: 99%

Harnessing low-density lipoprotein receptor protein 6 (LRP6) genetic variation and Wnt signaling for innovative diagnostics in complex diseases

et al. 2017

Pharmacogenomics J

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“…Some scholars have detected the coding genes of seven key enzymes in the mevalonate pathway, including Mevalonate kinase (MK), Phosphomevalonate kinase (PMVK), Mevalonate decarboxylase (MVD), Isopentenyl pyrophosphate isomerase (IPI), Geranylgeranyl pyrophosphate synthase 1 (GGPS1), Farnesyl pyrophosphate synthase (FDPS) and Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), and three genes of OPG/RANKL/RANK system, a total of 67 tag SNPs, and found that the response to alendronate is significantly associated with the patient's genetic background. [6][7][8][9][10][11] Some enzymes in other pathways of bone metabolism also showed high correlation, such as SOST. 6 Cathepsins are lysosomal cysteine proteases and papain family members.…”

Section: Introductionmentioning

confidence: 99%

Association Between CTSK Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density

Yuan,

Wang,

Liu

et al. 2023

PGPM

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Purpose The aim of this study was to explore the association between CTSK polymorphisms and the response to alendronate treatment in postmenopausal Chinese women with low bone mineral density. Patients and Methods In this study, 460 postmenopausal women from Shanghai were included. All of them were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for a year. Four tag single nucleotide polymorphisms (SNPs) in CTSK gene were genotyped. Bone mineral densities of lumbar spine (L1-L4), femoral neck and total hip were measured at baseline and after 12 months of treatment, respectively. Results After 1-year of treatment, there was no significant differences in BMI between baseline and follow-up. After alendronate treatment, the BMD of L1–4, femoral neck and total hip all increased significantly (all P < 0.001), with average increases of 4.33 ± 6.42%, 1.85 ± 4.20%, and 2.36 ± 3.79%, respectively. There was no significant difference in BMD at L1-L4, the femoral neck and total hip between different genotype groups at baseline ( P >0.05). After 1-year treatment with alendronate, rs12746973 and rs10847 were associated with the % change of BMD at L1-L4 ( P =0.038) and % change of BMD at femoral neck ( P =0.038), respectively. Furthermore, rs10847 was associated with BMD response at femoral neck ( P =0.013). However, the associations were not significant after Bonferroni correction. Conclusion We concluded that the common variations of CTSK gene were potentially associated with the therapeutic response to alendronate treatment in Chinese women with low bone mineral density. However, further validation is needed.

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The Analysis of DKK1 Polymorphisms in Relation to Skeletal Phenotypes and Bone Response to Alendronate Treatment in Chinese Postmenopausal Women

Abstract: DKK1 polymorphisms may correlate to baseline BMD and serum β-CTX levels, but present a weak effect on the response to alendronate.

Cited by 7 publications

References 34 publications

Genetic Polymorphisms of Nuclear Factor-κB Family Affect the Bone Mineral Density Response to Zoledronic Acid Therapy in Postmenopausal Chinese Women

Genetic Polymorphisms of Nuclear Factor-κB Family Affect the Bone Mineral Density Response to Zoledronic Acid Therapy in Postmenopausal Chinese Women

Harnessing low-density lipoprotein receptor protein 6 (LRP6) genetic variation and Wnt signaling for innovative diagnostics in complex diseases

Association Between CTSK Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density

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