title: Genetic polymorphisms in the mevalonate pathway affect the therapeutic response to alendronate treatment in postmenopausal Chinese women with low bone mineral density.
abstract: Alendronate is an antiosteoporotic drug that targets the mevalonate pathway. To investigate whether the genetic variations in this pathway affect the clinical efficacy of alendronate in postmenopausal Chinese women with osteopenia or osteoporosis, 23 single-nucleotide polymorphisms (SNPs) in 7 genes were genotyped in 500 patients treated with alendronate for 12 months. Bone mineral density (BMD) was measured at baseline and after 12 months. The rs10161126 SNP in the 3' flanking region of MVK and the GTCCA haplotype in FDFT1 were significantly associated with therapeutic response. A 6.6% increase in BMD in the lumbar spine was observed in the GG homozygotes of rs10161126; AG heterozygotes and AA homozygotes experienced a 4.4 and 4.5% increase, respectively. The odds ratio (95% confidence interval) of G allele carriers to be responders in lumbar spine BMD was 2.06 (1.08-6.41). GTCCA haplotype in FDFT1 was more frequently detected in the group of responders than in the group of non-responders at the total hip (2.6 vs 0.5%, P=0.009). Therefore, MVK and FDFT1 polymorphisms are genetic determinants for BMD response to alendronate therapy in postmenopausal Chinese women.
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: J-W
authors.initials: JW
authors.lastname: He
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Yue
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: W-W
authors.initials: WW
authors.lastname: Hu
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: J-M
authors.initials: JM
authors.lastname: Gu
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Shao
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: W-Z
authors.initials: WZ
authors.lastname: Fu
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Hu
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: 1] Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China [2] Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
authors.forename: Z-L
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D000368:Aged; D019386:Alendronate / Q000627:therapeutic use*; D000483:Alleles; D044466:Asian People / Q000235:genetics; D015519:Bone Density / Q000187:drug effects* / Q000235:genetics; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism*; D010024:Osteoporosis / Q000188:drug therapy / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause / Q000187:drug effects* / Q000235:genetics*
chemical_list: D050071:Bone Density Conservation Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D008798:Mevalonic Acid; D019386:Alendronate