title: Polymorphisms of the farnesyl diphosphate synthase gene modulate bone changes in response to atorvastatin.
abstract: Although their primary therapeutic indications are different, aminobisphosphonates and statins target enzymes in the mevalonate pathway, which is critical for bone homeostasis. Previous studies have shown that some polymorphisms of the gene encoding farnesyl diphosphate synthase (FDPS), the main target of aminobisphosphonates, modulate the response to these drugs. In this study, we explored whether those single nucleotide polymorphisms (SNPs) also influence the changes in bone mineral density (BMD) following therapy with statins. Sixty-six patients with coronary heart disease were studied at baseline and after 1-year therapy with atorvastatin. BMD was measured by DXA. Three SNPs of the FDPS gene (rs2297480, rs11264359 and rs17367421) were analyzed by using Taqman assays. The results showed that there was no association between the SNPs and basal BMD. However, rs2297480 and rs11264359 alleles, which are in linkage disequilibrium, were associated with changes in hip BMD following atorvastatin therapy. Thus, patients with AA genotype at the rs2297480 locus had a 0.8 ± 0.8 % increase in BMD at the femoral neck, whereas in patients with AC/CC genotypes, BMD showed a 2.3 ± 0.8 % decrease (p = 0.02). Similar results were obtained regarding changes of BMD at the femoral trochanter and when alleles at the rs11264359 locus were analyzed. However, there was no association between BMD and rs17367421 alleles. In conclusion, these results suggest that polymorphisms of the FDPS gene may influence the bone response to various drugs targeting the mevalonate pathway, including not only aminobisphosphonates but also statins.
authors: Department of Internal Medicine, Hospital Universitario Río Hortega, University of Valladolid, c/Dulzaina 2, 47010, Valladolid, Spain, castrv@terra.com.
authors: José L
authors: JL
authors: Pérez-Castrillón
authors: María T
authors: MT
authors: Zarrabeitia
authors: Laura
authors: L
authors: Abad
authors: Gemma
authors: G
authors: Vega
authors: Marta
authors: M
authors: Ruiz-Mambrilla
authors: Manuel
authors: M
authors: Gonzalez-Sagredo
authors: Antonio
authors: A
authors: Dueñas-Laita
authors: José A
authors: JA
authors: Riancho
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000069059:Atorvastatin; D015519:Bone Density / Q000187:drug effects*; D003327:Coronary Disease / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000201:enzymology; D005787:Gene Frequency; D005838:Genotype; D051228:Geranyltranstransferase / Q000235:genetics* / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D051228:Geranyltranstransferase