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慢性阻塞性肺疾病患者维生素D受体基因多态性与骨质疏松症的相关性

Association between vitamin D receptor polymorphisms and osteoporosis in patients with COPD.

作者信息

Kim Sei Won, Lee Jong Min, Ha Jick Hwan, Kang Hyeon Hui, Rhee Chin Kook, Kim Jin Woo, Moon Hwa Sik, Baek Ki Hyun, Lee Sang Haak

机构信息

Division of Pulmonology, Critical Care and Sleep Medicine, The Catholic University of Korea, Seoul, Korea.

Division of Endocrinology and Metabolism, Department of Internal Medicine, St Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

出版信息

Int J Chron Obstruct Pulmon Dis. 2015 Sep 4;10:1809-17. doi: 10.2147/COPD.S91576. eCollection 2015.

Abstract

BACKGROUND

Patients with COPD are at an increased risk of osteoporosis. Although many studies have addressed the relationship between the vitamin D receptor (VDR) polymorphisms and bone health, this relationship has not been fully investigated in patients with COPD. In this study, we investigated the association of VDR polymorphisms with bone mineral density (BMD) and other clinical parameters in patients with COPD.

PATIENTS AND METHODS

In total, 200 patients with COPD were included in this study. The VDR polymorphisms rs1544410 (A/G-BsmI), rs7975232 (A/C-ApaI), rs731236 (C/T-TaqI), and rs10735810 (C/T-FokI) were determined by Sanger sequencing using blood DNA samples. BMD of the lumbar vertebra and the femoral neck was measured by dual-energy X-ray absorptiometry. Other clinical parameters were also evaluated. Haplotype and multivariate analyses were also performed.

RESULTS

Sex, body mass index, steroid use, percentage of forced expiratory volume in 1 second (FEV1), alkaline phosphatase, and 25-hydroxyvitamin D significantly influenced the risk of osteoporosis. Patients with osteoporosis were more likely to carry the rs7975232 C allele compared to normal patients with BMD. Haplotypes GCT and GAT were related to osteoporosis. Patients without the haplotype GAT allele showed a significantly lower T-score at the femoral neck and an increased risk of osteoporosis (odds ratio [OR]= 2.78, 95% confidence interval [CI]= 1.20-6.48, P=0.018) compared with carriers in the dominant model.

CONCLUSION

Genetic variations in VDR are significantly associated with osteoporosis among patients with COPD. Further studies are required to confirm the role of the VDR polymorphisms in osteoporosis among patients with COPD.

摘要

背景

慢性阻塞性肺疾病(COPD)患者患骨质疏松症的风险增加。尽管许多研究探讨了维生素D受体(VDR)基因多态性与骨骼健康之间的关系,但在COPD患者中这一关系尚未得到充分研究。在本研究中,我们调查了COPD患者中VDR基因多态性与骨密度(BMD)及其他临床参数之间的关联。

患者与方法

本研究共纳入200例COPD患者。使用血液DNA样本通过桑格测序法测定VDR基因多态性rs1544410(A/G - BsmI)、rs7975232(A/C - ApaI)、rs731236(C/T - TaqI)和rs10735810(C/T - FokI)。采用双能X线吸收法测量腰椎和股骨颈的骨密度。还评估了其他临床参数。同时进行了单倍型和多变量分析。

结果

性别、体重指数、类固醇使用情况、1秒用力呼气容积(FEV1)百分比、碱性磷酸酶和25 - 羟基维生素D显著影响骨质疏松症的风险。与骨密度正常的患者相比,骨质疏松症患者更有可能携带rs7975232 C等位基因。单倍型GCT和GAT与骨质疏松症相关。在显性模型中,不携带单倍型GAT等位基因的患者股骨颈T值显著较低,患骨质疏松症的风险增加(优势比[OR]=2.78,95%置信区间[CI]=1.20 - 6.48,P = 0.018)。

结论

COPD患者中VDR基因的遗传变异与骨质疏松症显著相关。需要进一步研究以证实VDR基因多态性在COPD患者骨质疏松症中的作用。

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