Study on the genetic association of LRP5 gene polymorphism and susceptibility to osteoporosis in patients with chronic obstructive pulmonary disease_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LI Kao ¹ , SONG Shujun ² , ZHU Minli ¹ , WANG Ruijuan ¹ , DONG Jin ³ , YAN Ruyi ⁴ ,  FENG Kai ²

1. Department of Respiration, PLA Strategic Support Force Characteristic Medical Center, Beijing 100101, P. R. China;
2. Center for Special Medicine and Experimental Research, PLA Strategic Support Force Characteristic Medical Center, Beijing 100101, P. R. China;
3. Department of Clinical Laboratory, PLA Strategic Support Force Characteristic Medical Center, Beijing 100101, P. R. China;
4. Department of Radiology, PLA Strategic Support Force Characteristic Medical Center, Beijing 100101, P. R. China;

Corresponding?author：

FENG Kai, Email: fkjiafp@126.com

Keywords：

Pulmonary disease, chronic obstructive; Osteoporosis; Low-density lipoprotein receptor-related protein 5 (LRP5) gene; Single nucleotide polymorphism

DOI：

10.7507/1671-6205.201904004

Video：

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Objective To understand the genetics associations between low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms and susceptibility of osteoporosis in patients with chronic obstructive pulmonary disease (COPD).Methods Three hundred and seventy-nine patients with acute exacerbation of COPD were divided into groups of non osteoporosis and osteoporosis. Genomic DNA was extracted from all patients. UCSC genome browser and Haploview 4.2 software were used to screen tag single nucleotide polymorphisms (tagSNP) of LRP5 gene. The tagSNP was genotyped by Sequenom MassARRAY SNP detection method. Logistic regression were used to analysis the odds ratio (OR) values and confidence intervals (CI) of each SNP in different genetic models to assess the association between single nucleotide polymorphisms in LRP5 gene and osteoporosis in COPD patients.Results Eight tagSNPs of LRP5 gene (rs312016 T/C, rs312017 C/T, rs312018 A/G, rs3736228 C/T, rs901823 T/C, rs589963 G/A, rs638051 A/G, rs671494 C/A) were selected for association analysis. Patients of rs901823 carrying C/C genotype had a higher risk of osteoporosis than those carrying T/T and C/T genotypes in COPD patients (in recessive mode, C/C vs. T/T+C/T, OR=9.42, 95%CI=2.01–44.29), P=0.000 431 8).Conclusions There is a significant association between rs901823 of LRP5 gene and osteoporosis in patients with COPD. Further studies are needed to discover the mechanism of LRP5 gene polymorphism in the pathogenesis of osteoporosis in COPD patients.

Citation： LI Kao, SONG Shujun, ZHU Minli, WANG Ruijuan, DONG Jin, YAN Ruyi, FENG Kai. Study on the genetic association of LRP5 gene polymorphism and susceptibility to osteoporosis in patients with chronic obstructive pulmonary disease. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(6): 515-521. doi: 10.7507/1671-6205.201904004 Copy

1.	Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 2012, 380(9859): 2095-2128.
2.	Kokturk N, Gurgun A, Sen E, et al. The View of the Turkish Thoracic Society on the Report of the GOLD 2017 Global Strategy for the Diagnosis, Management, and Prevention of COPD. Turk Thorac J, 2017, 18(2): 57-64.
3.	Sassi R, Sahli H, Souissi C, et al. Association of LRP5 genotypes with osteoporosis in Tunisian post-menopausal women. BMC Musculoskelet Disord, 2014, 15: 144.
4.	Xu GY, Qiu Y, Mao HJ. Common polymorphism in the LRP5 gene may increase the risk of bone fracture and osteoporosis. Biomed Res Int, 2014, 2014: 290531.
5.	Xuan M, Wang Y, Wang W, et al. Association of LRP5 gene polymorphism with type 2 diabetes mellitus and osteoporosis in postmenopausal women. Int J Clin Exp Med, 2014, 7(1): 247-254.
6.	李考, 王萍, 閆如意, 等. 慢性阻塞性肺疾病患者椎骨的 CT 值與骨密度的關系. 中華結核和呼吸雜志, 2018, 41(5): 341-344.
7.	毛澤慶, 徐香玖, 張恒, 等. 多層螺旋 CT 評價慢性阻塞性肺病患者骨質疏松的臨床應用研究. 蘭州大學學報(醫學版), 2015, 41(4): 40-43, 47.
8.	李考, 馮凱, 王萍, 等. VDR 基因單核苷酸多態性與慢性阻塞性肺疾病并發骨質疏松的關系. 解放軍醫學雜志, 2019, 44(6): 484-492.
9.	張騰飛, 周鋼橋, 岳茂興, 等. 白介素 33 基因多態性與膿毒癥的關聯研究. 中華急診醫學雜志, 2016, 25(2): 160-166.
10.	李增艷, 卜小寧, 苗苗, 等. 穩定期慢性阻塞性肺疾病患者的去脂質量指數與骨強度的關系. 中華結核和呼吸雜志, 2015, 38(1): 50-54.
11.	Schreiber JJ, Anderson PA, Rosas HG, et al. Hounsfield units for assessing bone mineral density and strength: a tool for osteoporosis management. J Bone Joint Surg Am, 2011, 93(11): 1057-1063.
12.	Zhou PR, Liu HJ, Liao EY, et al. LRP5 polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis. Pharmacogenomics, 2014, 15(6): 821-831.
13.	Koay MA, Tobias JH, Leary SD, et al. The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood. Calcif Tissue Int, 2007, 81(1): 1-9.
14.	Furuya T, Urano T, Ikari K, et al. A1330V polymorphism of low-density lipoprotein receptor-related protein 5 gene and self-reported incident fractures in Japanese female patients with rheumatoid arthritis. Mod Rheumatol, 2009, 19(2): 140-146.
15.	Funakoshi Y, Omori H, Yada H, et al. A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density in Japanese male workers. Environ Health Prev Med, 2011, 16(2): 106-112.
16.	Markatseli AE, Hatzi E, Bouba I, et al. Association of the A1330V and V667M polymorphisms of LRP5 with bone mineral density in Greek peri- and postmenopausal women. Maturitas, 2011, 70(2): 188-193.
17.	Chubachi S, Nakamura H, Sasaki M, et al. Polymorphism of LRP5 gene and emphysema severity are associated with osteoporosis in Japanese patients with or at risk for COPD. Respirology, 2015, 20(2): 286-295.

1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 2012, 380(9859): 2095-2128.
2. Kokturk N, Gurgun A, Sen E, et al. The View of the Turkish Thoracic Society on the Report of the GOLD 2017 Global Strategy for the Diagnosis, Management, and Prevention of COPD. Turk Thorac J, 2017, 18(2): 57-64.
3. Sassi R, Sahli H, Souissi C, et al. Association of LRP5 genotypes with osteoporosis in Tunisian post-menopausal women. BMC Musculoskelet Disord, 2014, 15: 144.
4. Xu GY, Qiu Y, Mao HJ. Common polymorphism in the LRP5 gene may increase the risk of bone fracture and osteoporosis. Biomed Res Int, 2014, 2014: 290531.
5. Xuan M, Wang Y, Wang W, et al. Association of LRP5 gene polymorphism with type 2 diabetes mellitus and osteoporosis in postmenopausal women. Int J Clin Exp Med, 2014, 7(1): 247-254.
6. 李考, 王萍, 閆如意, 等. 慢性阻塞性肺疾病患者椎骨的 CT 值與骨密度的關系. 中華結核和呼吸雜志, 2018, 41(5): 341-344.
7. 毛澤慶, 徐香玖, 張恒, 等. 多層螺旋 CT 評價慢性阻塞性肺病患者骨質疏松的臨床應用研究. 蘭州大學學報(醫學版), 2015, 41(4): 40-43, 47.
8. 李考, 馮凱, 王萍, 等. VDR 基因單核苷酸多態性與慢性阻塞性肺疾病并發骨質疏松的關系. 解放軍醫學雜志, 2019, 44(6): 484-492.
9. 張騰飛, 周鋼橋, 岳茂興, 等. 白介素 33 基因多態性與膿毒癥的關聯研究. 中華急診醫學雜志, 2016, 25(2): 160-166.
10. 李增艷, 卜小寧, 苗苗, 等. 穩定期慢性阻塞性肺疾病患者的去脂質量指數與骨強度的關系. 中華結核和呼吸雜志, 2015, 38(1): 50-54.
11. Schreiber JJ, Anderson PA, Rosas HG, et al. Hounsfield units for assessing bone mineral density and strength: a tool for osteoporosis management. J Bone Joint Surg Am, 2011, 93(11): 1057-1063.
12. Zhou PR, Liu HJ, Liao EY, et al. LRP5 polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis. Pharmacogenomics, 2014, 15(6): 821-831.
13. Koay MA, Tobias JH, Leary SD, et al. The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood. Calcif Tissue Int, 2007, 81(1): 1-9.
14. Furuya T, Urano T, Ikari K, et al. A1330V polymorphism of low-density lipoprotein receptor-related protein 5 gene and self-reported incident fractures in Japanese female patients with rheumatoid arthritis. Mod Rheumatol, 2009, 19(2): 140-146.
15. Funakoshi Y, Omori H, Yada H, et al. A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density in Japanese male workers. Environ Health Prev Med, 2011, 16(2): 106-112.
16. Markatseli AE, Hatzi E, Bouba I, et al. Association of the A1330V and V667M polymorphisms of LRP5 with bone mineral density in Greek peri- and postmenopausal women. Maturitas, 2011, 70(2): 188-193.
17. Chubachi S, Nakamura H, Sasaki M, et al. Polymorphism of LRP5 gene and emphysema severity are associated with osteoporosis in Japanese patients with or at risk for COPD. Respirology, 2015, 20(2): 286-295.

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