Relationship between polymorphism and mutation of LRP5 and SOST gene with bone metabolism in postmenopausal type 2 diabetic mellitus women in Shihezi,Xinjiang

doi:10.3969/j.issn.1006-7795.2022.02.018

Abstract

Abstract: Objective To explore the relationship between SOST gene and low density lipoprotein 5 (LRP5) gene polymorphisms and mutations and bone metabolism in postmenopausal T2DM women in Shihezi area, and to provide reference for the occurrence of postmenopausal T2DM with osteoporosis (OP). Methods The subjects were divided into two groups: normal bone mass group and abnormal bone mass group. Then based on whether they were with type 2 diabetes mellitus(T2DM),the patients were divided into four sub groups:normal glucose with bone mass group,normal glucose with abnormal bone mass group,T2DM group with normal bone mass group,and T2DM with abnormal bone mass group. Calcium (Ca), fasting plasma glucose (FPG), triacylglycerol(TG), alkaline phosphatase(ALP) etc. clinical biochemical data were determined by Automatic biochemical analyzer; dual-energy X-ray absorptiometry (DXA) method to detect bone mineral density (BMD); and the polymorphisms of the LRP5 and SOST gene were detected by time-of-flight mass spectrometry (TOF-MS). Results (1)The rs901825 polymorphism of the LRP5 genotype distribution was statistically significant (P<0.05) in group D compared with group A. The rs7125942 polymorphism of the LRP5 genotype distribution was statistically significant (P<0.05) in group B compared with group A. (2)In group D, at the SOST rs10534024 site, BMD of TCC.DEL/TCC.TCC genotype (mutant) was lower than that of DEL.DEL genotype (wild-type)(0.69±0.13 vs 0.76±0.10,P<0.05); LRP5 gene rs7125942 locus, on TG, CC genotype (wild type) and CG genotype (mutant type) were 4.12±0.79 and 3.22±1.04, respectively, the former was significantly higher (P<0.01); In group B, at the SOST rs851054 site, TG of GG genotype (wild-type) was higher than that of AG/AA genotype (Mutant) (2.11±1.19 vs 1.30±0.80,P<0.05). (3)Interaction analysis showed that the interaction between rs851054 of SOST gene and rs7125942 of LRP5 gene affected BMD(femoral neck) (P<0.05). The interaction between SOST gene and LRP5 gene has an effect on BMD (femoral neck) (P<0.01). Multiple linear regression analysis found rs10534024 of SOST gene, TG and body mass index were positively correlated with BMD(L1-4). Rs7125942 of LRP5 gene and menopause duration were negatively correlated with BMD (femoral neck). Conclusion The polymorphism and frequency distribution of LRP5 gene rs901825 and rs7125942 in postmenopausal women in Shihezi may be related to bone metabolism; The genetic mutation of rs7125942 locus of LRP5 gene may be related to lipid metabolism of postmenopausal women. The mutation of rs10534024 of SOST gene may be related to BMD in postmenopausal women in Shihezi. The interaction between SOST gene and LRP5 gene is a risk factor for BMD (femoral neck) reduction.

Key words: LRP5 gene polymorphism, SOST gene polymorphism, type 2 diabetes mellitus, osteoporosis, bone mineral density, postmenopausal women

CLC Number:

R587.1

Song Limin, Li Siyuan, Li Jun, Zhao Huirong, Li Jiajia, Wang Shuang. Relationship between polymorphism and mutation of LRP5 and SOST gene with bone metabolism in postmenopausal type 2 diabetic mellitus women in Shihezi,Xinjiang[J]. Journal of Capital Medical University, 2022, 43(2): 269-274.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2022.02.018

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2022/V43/I2/269

References

[1] Niyazy M M. The role of FAT MASS and obesity association locus “Fto” gene polymorphism in susceptibility to development of type 2 diabetes and obesity in selected Sudanese population[D].Khartoum:University of Khartoum,2015.
[2] McClung M R, Wagman R B, Miller P D, et al. Observations following discontinuation of long-term denosumab therapy[J]. Osteoporos Int, 2017, 28(5): 1723-1732.
[3] 易伟莲, 廖德权, 林柏云, 等. 绝经后骨质疏松症患者性激素、细胞因子及骨代谢指标的变化及关系[J]. 检验医学, 2012, 27(4): 296-298.
[4] 徐伟丽, 牛玲玲, 王文侠, 等. 经典Wnt信号通路对骨代谢的调节作用[J]. 中国骨质疏松杂志, 2016, 22(3): 376-380.
[5] You H F, Zhao J Z, Zhai Y J, et al. Association between low-density lipoprotein receptor-related protein 5 polymorphisms and type 2 diabetes mellitus in Han Chinese: a case-control study[J]. Biomed Environ Sci, 2015, 28(7): 510-517.
[6] 渠昕, 楚淑芳, 赵恒侠, 等. 滋肾降糖丸对肾阴虚证2型糖尿病患者血清硬化蛋白的影响[J]. 新中医, 2018, 50(5): 51-54.
[7] Gaudio A, Privitera F, Pulvirenti I, et al. The relationship between inhibitors of the Wnt signalling pathway (sclerostin and Dickkopf-1) and carotid intima-media thickness in postmenopausal women with type 2 diabetes mellitus[J]. Diab Vasc Dis Res, 2014, 11(1): 48-52.
[8] Alberti K G, Zimmet P Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation[J]. Diabet Med,1998,15(7):539-553.
[9] Kanis J A. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group[J].Osteoporos Int,1994,4(6):368-381.
[10] Mohd-Tahir N A, Li S C. Economic burden of osteoporosis-related hip fracture in Asia: a systematic review[J]. Osteoporos Int, 2017, 28(7): 2035-2044.
[11] Raška I Jr, Rašková M, Zikán V, et al. Prevalence and risk factors of osteoporosis in postmenopausal women with type 2 diabetes mellitus[J]. Cent Eur J Public Health, 2017, 25(1): 3-10.
[12] Bonaccorsi G, Messina C, Cervellati C, et al. Fracture risk assessment in postmenopausal women with diabetes: comparison between DeFRA and FRAX tools[J]. Gynecol Endocrinol, 2018, 34(5): 404-408.
[13] Astiazarán M C, Cervantes-Sodi M, Rebolledo-Enríquez E, et al. Novel homozygous LRP5 mutations in Mexican patients with osteoporosis-pseudoglioma syndrome[J]. Genet Test Mol Biomarkers, 2017, 21(12): 742-746.
[14] Uitterlinden A G, Arp P P, Paeper B W, et al. Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites[J]. Am J Hum Genet, 2004, 75(6): 1032-1045.
[15] Balemans W, Foernzler D, Parsons C, et al. Lack of association between the SOST gene and bone mineral density in perimenopausal women: analysis of five polymorphisms[J]. Bone, 2002, 31(4): 515-519.
[16] Bijelic R, Balaban J, Milicevic S. Correlation of the lipid profile, BMI and bone mineral density in postmenopausal women[J]. Mater Sociomed, 2016, 28(6): 412-415.
[17] Wang J J, Yan G L, Zhang J F, et al. Association of LRP5, TCF7L2, and GCG variants and type 2 diabetes mellitus as well as fasting plasma glucose and lipid metabolism indexes[J]. Hum Immunol, 2015, 76(5): 339-343.
[18] Piters E, De Freitas F, Nielsen T L, et al. Association study of polymorphisms in the SOST gene region and parameters of bone strength and body composition in both young and elderly men: data from the Odense Androgen Study[J]. Calcif Tissue Int, 2012, 90(1): 30-39.