rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2016-49-52rsp-2169Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHГенетические полиморфизмы фарнезил-дифосфат синтазы (FDPS) и геранилгеранил-дифосфат синтазы (GGSP1) и эффективность терапии бисфосфонатами у российских женщин с постменопаузальным остеопорозом: пилотное исследованиеFARNESYL DIPHOSPHATE SYNTHASE (FDRS) AND GERANYLGERANYL DIPHOSPHATE SYNTHASE (GGSP1) GENE POLYMORPHISMS AND EFFICIENCY OF THERAPY WITH BISPHOSPHONATES IN RUSSIAN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS: A PILOT STUDYКрыловМ. Ю.KrylovM. Yu.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

mekry@yandex.ruНикитинскаяО. А.NikitinskayaO. A.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

СамаркинаЕ. Ю.SamarkinaE. Yu.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ДеминН. В.DeminN. V.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ТоропцоваН. В.ToroptsovaN. V.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ФГБНУ Научно-исследовательский институт ревматологии им. В.А. НасоновойРоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation2016230320165414952Copyright © Крылов М.Ю., Никитинская О.А., Самаркина Е.Ю., Демин Н.В., Торопцова Н.В., 20162016Крылов М.Ю., Никитинская О.А., Самаркина Е.Ю., Демин Н.В., Торопцова Н.В.Krylov M.Y., Nikitinskaya O.A., Samarkina E.Y., Demin N.V., Toroptsova N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2169

Минеральная плотность кости (МРК) на 60–80% обусловлена генетическими факторами, которые являются важным наследственным компонентом, определяющим предрасположенность к остеопорозу (ОП). Ранее было показано влияние отдельных полиморфных генов на эффективность проводимой противоостеопоротической терапии.

Цель исследования – изучить влияние полиморфизмов генов фарнезил-дифосфат синтазы (FDPS) и геранилгеранил-дифосфат синтазы 1 (GGPS1) на динамику МПК на фоне 12-месячной терапии бисфосфонатами (БФ) у женщин с постменопаузальным ОП.

Материал и методы

Материал и методы. В исследование включены 53 женщины с ОП. МПК в позвоночнике и проксимальном отделе бедра определяли с помощью рентгеновской денситометрии до и после лечения БФ. Полиморфизмы -99A/C и -8188T ins/del генов FDPS и GGPS1 исследованы методом полимеразной цепной реакции в режиме реального времени.

Результаты и обсуждение

Результаты и обсуждение. Динамика МПК была менее выражена у женщин с аллелью С полиморфизма -99A/C гена FDPS по сравнению с носителями генотипа АА: 2,3±3,6 и 4,4±3,8% (р=0,062) в позвоночнике; 0,6±3,1 и 2,8±4,5% (р=0,075) – в шейке бедра; 0,5±2,9 и 2,5±2,8% (р=0,020) – в области всего бедра соответственно. По данным денситометрии шейки бедра наблюдался значительно более слабый ответ на лечение БФ у больных – носителей мутантного генотипа del/del полиморфизма -8188T ins/del гена GGSP1 по сравнению с диким генотипом ins/ins (0,8±4,2 и 4,1±2,5% соответственно; р=0,030). В других областях измерения МПК достоверных различий для данного полиморфизма не выявлено.

Выводы

Выводы. Представленное пилотное исследование показало, что изученные полиморфизмы генов FDPS и GGSP1 могут быть предикторами ответа на терапию БФ у больных ОП. Для подтверждения наших результатов необходимы дальнейшие исследования, которые будут способствовать выбору наиболее эффективной терапии данного заболевания.

Genetic factors that are an important hereditary component determining a predisposition to osteoporosis (OP) are 60–80% responsible for bone mineral density (BMD). Some polymorphic genes have been previously shown to affect the efficiency of performed anti-osteoporotic therapy.

Objective

Objective: to study the impact of farnesyl diphosphate synthase (FDRS) and geranylgeranyl diphosphate synthase (GGSPI) gene polymorphisms on BMD changes during 12-month therapy with bisphosphonates (BP) in women with postmenopausal OP.

Subjects and methods

Subjects and methods. The investigation enrolled 53 women with OP. Spine and proximal femur BMD was determined using X-ray densitometry before and after BP treatment. The -99A/C and -8188T ins/del polymorphisms in the FDPS and GGPS1 genes were investigated using real-time polymerase chain reaction.

Results and discussion

Results and discussion. The BMD changes were less marked in women with the C allele of C/T -99/C polymorphism in the FDPS gene than those in carriers of the genotype AA: 2.3±3.6 and 4.4±3.8% (р = 0.062) in the spine; 0.6±3.1 and 2.8±4.5% (р = 0.075) in the femoral neck; 0.5±2.9 and 2.5±2.8% (р = 0.020) in the entire femur, respectively. Femoral neck densitometry showed a significantly weaker response to BP treatment in the patients carrying the mutant genotype del/del of GGSP1 -8188T ins/del polymorphism than in those with the wild-type genotype ins/ins (0.8±4.2 and 4.1±2.5%, respectively; р = 0.030). No significant differences for this polymorphism were found in other areas of BMD measurement.

Conclusion

Conclusion. The described pilot study has indicated that the examined FDPS and GGSP1 gene polymorphisms may be predictors for a response to BP therapy in patients with OP. Further investigations that will contribute to the choice of the most effective therapy for this disease are needed to confirm our results.

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The authors declare that there are no conflicts of interest present.