Genetic polymorphisms in the mevalonate pathway affect the therapeutic response to alendronate treatment in postmenopausal Chinese women with low bone mineral density
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...
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Published in | The pharmacogenomics journal Vol. 15; no. 2; pp. 158 - 164 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.04.2015
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1470-269X 1473-1150 |
DOI: | 10.1038/tpj.2014.52 |