Polymorphism of LRP4 Gene (rs9667108) Among Post Menopause Women with Osteoporosis

Overview

Journal Iran J Public Health

Date 2023 Aug 8

PMID 37551184

Authors

Saeid Kavoosian

Alimohammad Asgharian

Mohsen Asouri

Sadegh Fattahi

Galia Amirbozorgi

Ali Kheirandish

Sajad Abolfazli

Maryam Lotfi

Nima Ebrahimi

Ramin Ataee

Affiliations

Soon will be listed here.

Abstract

Background: Many studies have been done to identify the factors that influence the development and progression of osteoporosis. One genetic factor is polymorphisms of gene. Regarding the lack of comprehensive study on polymorphisms of gene in the north of Iran, mainly Mazandaran Province, we decided to investigate the polymorphism of this gene in postmenopausal women with osteoporosis.

Methods: This case-control study has been conducted at GhaemShahr Valiasr Hospital on 100 female patients with osteoporosis (average age of 58.1) and 90 healthy females without osteoporosis (average age of 55.2). After sampling and extraction of genomic DNA via of the salt deposition method, the genotype and SNP (rs9667108) polymorphism of gene were evaluated with the PCR-RFLP method. Restriction enzymes cut the PCR products. In order to identify patients, their bone mineral density was tested by the DEXA method. The results of digestion (digestion enzyme) were analyzed by MedCalc, SPSS software, Hardy-Weinberg equilibrium, and Chi2.

Results: The statistical analysis has shown the significant relationship between SNP (rs9667108) polymorphism and the risk of osteoporosis disease in patients and control groups (<0.05). In SNP (rs9667108), the GC genotype, compared to GG, increased the risk of disease significantly (1.556 time). Similarly, CC genotype, compared to GG genotype, increased the risk of this disease by 2.091 time.

Conclusion: The existence of mutation in the gene could increase susceptibility to osteoporosis disease. Moreover, determining this patient's genotype in SNP (rs9667108) can be used to identify individuals who are in endanger osteoporosis.

References

Morris C, Cabral D, Cheng H, Katz J, Finkelstein J, Avorn J . Patterns of bone mineral density testing: current guidelines, testing rates, and interventions. J Gen Intern Med. 2004; 19(7):783-90. PMC: 1492483. DOI: 10.1111/j.1525-1497.2004.30240.x. View

Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson B, Hsu Y, Richards J . Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet. 2009; 41(11):1199-206. PMC: 2783489. DOI: 10.1038/ng.446. View

Spatz J, Fields E, Yu E, Divieti Pajevic P, Bouxsein M, Sibonga J . Serum sclerostin increases in healthy adult men during bed rest. J Clin Endocrinol Metab. 2012; 97(9):E1736-40. PMC: 3431567. DOI: 10.1210/jc.2012-1579. View

Li Y, Pawlik B, Elcioglu N, Aglan M, Kayserili H, Yigit G . LRP4 mutations alter Wnt/beta-catenin signaling and cause limb and kidney malformations in Cenani-Lenz syndrome. Am J Hum Genet. 2010; 86(5):696-706. PMC: 2869043. DOI: 10.1016/j.ajhg.2010.03.004. View

Nguyen V . Osteoporosis prevention and osteoporosis exercise in community-based public health programs. Osteoporos Sarcopenia. 2019; 3(1):18-31. PMC: 6372810. DOI: 10.1016/j.afos.2016.11.004. View

Golchin M, Heidari L, Ghaderian S, Akhavan-Niaki H . Osteoporosis: A Silent Disease with Complex Genetic Contribution. J Genet Genomics. 2016; 43(2):49-61. DOI: 10.1016/j.jgg.2015.12.001. View

Watts N, Adler R, Bilezikian J, Drake M, Eastell R, Orwoll E . Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012; 97(6):1802-22. DOI: 10.1210/jc.2011-3045. View

Weatherbee S, Anderson K, Niswander L . LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction. Development. 2006; 133(24):4993-5000. DOI: 10.1242/dev.02696. View

Robling A, Niziolek P, Baldridge L, Condon K, Allen M, Alam I . Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2007; 283(9):5866-75. DOI: 10.1074/jbc.M705092200. View

10.

Loh K, Shong H . Osteoporosis: primary prevention in the community. Med J Malaysia. 2008; 62(4):355-7. View

11.

Camacho P, Petak S, Binkley N, Clarke B, Harris S, Hurley D . AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS - 2016--EXECUTIVE SUMMARY. Endocr Pract. 2016; 22(9):1111-8. DOI: 10.4158/EP161435.ESGL. View

12.

Leupin O, Piters E, Halleux C, Hu S, Kramer I, Morvan F . Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem. 2011; 286(22):19489-500. PMC: 3103328. DOI: 10.1074/jbc.M110.190330. View

13.

Lara-Castillo N, Johnson M . LRP receptor family member associated bone disease. Rev Endocr Metab Disord. 2015; 16(2):141-8. PMC: 4553092. DOI: 10.1007/s11154-015-9315-2. View

14.

Spatz J, Wein M, Gooi J, Qu Y, Garr J, Liu S . The Wnt Inhibitor Sclerostin Is Up-regulated by Mechanical Unloading in Osteocytes in Vitro. J Biol Chem. 2015; 290(27):16744-58. PMC: 4505423. DOI: 10.1074/jbc.M114.628313. View

15.

Wang C, Zhang Z, Zhang H, He J, Gu J, Hu W . Susceptibility genes for osteoporotic fracture in postmenopausal Chinese women. J Bone Miner Res. 2012; 27(12):2582-91. DOI: 10.1002/jbmr.1711. View

16.

Yang T, Shen H, Liu A, Dong S, Zhang L, Deng F . A road map for understanding molecular and genetic determinants of osteoporosis. Nat Rev Endocrinol. 2019; 16(2):91-103. PMC: 6980376. DOI: 10.1038/s41574-019-0282-7. View

17.

Nordberg R, Mellor L, Krause A, Donahue H, Loboa E . LRP receptors in chondrocytes are modulated by simulated microgravity and cyclic hydrostatic pressure. PLoS One. 2019; 14(10):e0223245. PMC: 6777824. DOI: 10.1371/journal.pone.0223245. View

18.

Johnson E, Hammer R, Herz J . Abnormal development of the apical ectodermal ridge and polysyndactyly in Megf7-deficient mice. Hum Mol Genet. 2005; 14(22):3523-38. DOI: 10.1093/hmg/ddi381. View

19.

Pai M . Osteoporosis Prevention and Management. J Obstet Gynaecol India. 2017; 67(4):237-242. PMC: 5491422. DOI: 10.1007/s13224-017-0994-3. View

20.

Chang M, Kramer I, Huber T, Kinzel B, Guth-Gundel S, Leupin O . Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels. Proc Natl Acad Sci U S A. 2014; 111(48):E5187-95. PMC: 4260537. DOI: 10.1073/pnas.1413828111. View