Association of farnesyl diphosphate synthase polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis

被引：9

作者：

Liu Yi ^{[1
]}

Liu Haijuan ^{[3
]}

Li Mei ^{[1
]}

Zhou Peiran ^{[1
]}

Xing Xiaoping ^{[1
]}

Xia Weibo ^{[1
]}

Zhang Zhenlin ^{[4
]}

Liao Eryuan ^{[5
]}

Chen Decai ^{[6
]}

Liu Jian ^{[7
]}

Tao Tianzun ^{[8
]}

Wu Wen ^{[9
]}

Xu Ling ^{[2
]}

机构：

[1] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Endocrinol,Key Lab Endocrinol,Minist Hlth, Beijing 100730, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, Beijing 100730, Peoples R China

[3] Peoples Hosp Liaocheng, Dept Endocrinol, Liaocheng 252002, Shandong, Peoples R China

[4] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Dept Osteoporosis & Bone Dis, Metab Bone Dis & Genet Res Unit, Shanghai 200233, Peoples R China

[5] Cent S Univ, Xiangya Hosp 2, Inst Endocrinol & Metab, Changsha 410011, Hunan, Peoples R China

[6] Sichuan Univ, West China Hosp, Osteoporosis Educ Ctr, Dept Endocrinol, Chengdu 610041, Sichuan, Peoples R China

[7] Fourth Liberat Army Univ, Xijing Hosp, Dept Orthoped, Xian 710032, Shannxi, Peoples R China

[8] Harbin Med Univ, Affiliated Hosp 2, Dept Orthoped, Harbin 150081, Heilongjiang, Peoples R China

[9] Guangdong Gen Hosp, Dept Endocrinol, Guangzhou 510080, Guangdong, Peoples R China

来源：

CHINESE MEDICAL JOURNAL | 2014年 / 127卷 / 04期

基金：

中国国家自然科学基金;

关键词：

farnesyl diphosphate synthase polymorphism; alendronate; osteoporosis; pharmacogenomics; BONE-MINERAL DENSITY; THERAPY; PHARMACOGENOMICS; FRACTURE; RISK; BSMI;

D O I：

10.3760/cma.j.issn.0366-6999.20132382

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Genetic factors are important in the pathogenesis of osteoporosis, but less is known about the genetic determinants of osteoporosis treatment. We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase (FDPS) in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China. Methods The study group comprised 639 postmenopausal women aged (62.2 +/- 7.0) years with osteoporosis or osteopenia who had been randomly assigned to low dose group (70 mg/2w) or standard dose group (70 mg/w) of alendronate in this 1-year study. We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul. Before and after treatment, serum levels of calcium, phosphate, alkaline phosphatase (ALP), cross linked C-telopeptide of type I collagen (beta-CTX) were detected. Bone mineral density (BMD) at lumbar spine and proximal femur was measured. The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD, bone turnover biomarkers after the treatment. Results The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck, and patients with CC genotype had significantly higher baseline femoral neck BMD ((733.6 +/- 84.1) mg/crn(2)) than those with AC genotypes ((703.0 +/- 86.9) mg/cm(2)) and AA genotypes ((649.8 +/- 62.4) mg/cm(2)) (P < 0.01). No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS. The percentage change of serum ALP level was significantly lower in patients with CC genotype (-22.9%) than that in those with AC genotype (-24.1%) and AA genotype (-29.8%) of FDPS after 12 months of alendronate treatment (P < 0.05). Neither percentage change of BMD nor beta-CTX level after alendronate treatment had association with FDPS genotype. Conclusions FDPS gene was probably a candidate gene to predict femoral neck BMD at baseline. FDPS gene alleles could predict change percentage of ALP after treatment of alendronate, but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.

引用

页码：662 / 668

页数：7