Association between NF- κ B Signal Pathway-Related Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density

Xiaoyi Shen; Sasa Tan; Xianzhen Feng; Wenzhen Fu; Yunqiu Hu; Miao Li; Wenjie Wang; Hu Yuan; Li Liu; Chun Wang; Fei Hua

doi:10.1155/2022/2461716

Association between NF- κ B Signal Pathway-Related Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density

Evid Based Complement Alternat Med. 2022 Mar 24:2022:2461716. doi: 10.1155/2022/2461716. eCollection 2022.

Authors

Xiaoyi Shen^{1

2

3}, Sasa Tan³, Xianzhen Feng³, Wenzhen Fu², Yunqiu Hu², Miao Li², Wenjie Wang², Hu Yuan², Li Liu², Chun Wang², Fei Hua¹

Affiliations

¹ Department of Endocrinology, The Third Affiliated Hospital of Soochow University, 185, Juqian Street, Changzhou 213003, China.
² Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China.
³ Department of General Practice, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 111 Xianxia Road, Shanghai 200336, China.

Abstract

Background: Osteoporosis is a systemic bone disease characterized by reduction of bone content. Bisphosphonates are first-line treatments for osteoporosis, but they have variable effectiveness. Genetic factors may explain these differences. The NF-κB signaling pathway plays a key role in the regulation of bone metabolism. We aimed to determine whether genetic variations in the NF-κB signaling pathway affect the effectiveness of alendronate in postmenopausal Chinese women with low bone mass.

Methods: We recruited 455 postmenopausal Han Chinese women with primary osteoporosis or osteopenia aged 48-90 yrs who had experienced no spontaneous menses for at least 1 yr. All participants had dual X-ray absorptiometry (DEXA) bone mineral density (BMD) measurement at baseline and 1 yr after treatment. Treatment involved 1 yr administration of 70 mg oral alendronate weekly and 600 mg calcium and 125 IU of vitamin D daily. Thirteen tagSNPs in NF-κB1 (rs28362491, rs3774937, rs230521, rs230510, and rs4648068), RELA (rs7119750, rs11820062), and NLRC5 (rs289747, rs1566439, rs1684575, rs289726, rs289723, and rs41383) were chosen from the NCBI Locus Link and HapMap and genotyped individually. Genetic variation in these genes and the corresponding therapeutic response to alendronate treatment were analyzed.

Results: Among the 13 tagSNPs, rs289747 was significantly correlated with the BMD change rate at the femoral neck (P=0.048). This significance no longer existed after Bonferroni correction. We then performed principal component analysis (PCA) and found NLRC5 (rs289747 and rs1566439) were strongly correlated with alendronate efficacy in femoral phenotypes and were major components of BMD change values, particularly total hip and intertrochanteric phenotypes. Furthermore, the PLINK linear regression GLM model revealed that haplotype TT of RELA (rs7119750 and rs11820062) and ICCTA of NF-κB1 (rs28362491, rs3774937, rs230521, rs230510, and rs4648068) were associated with BMD of the total hip among each haplotype after 1 yr of treatment.

Conclusion: The NF-κB1, RELA, and NLRC5 genetic variations affect the therapeutic response of alendronate treatment for postmenopausal osteoporosis.