JAG1, MEF2C and BDNF polymorphisms associated with bone mineral density in women from Northern México
Abstract
Introduction: Osteoporosis is characterized by a low bone mineral density. Genetic composition is one of the most influential factors in determining bone mineral density (BMD). There are few studies on genes associated with BMD in the Mexican population.
Objective: To investigate the association of eight single nucleotide polymorphisms (SNP) of JAG1, MEF2C and BDNF genes with BMD in women of Northern México.
Materials and methods: This study involved 124 unrelated Mexican women between 40 and 80 years old. BMD was determined by dual X-ray absorptiometry. Genotyping was performed using allelic discrimination by real time PCR. We analyzed the SNP of JAG1 (rs6514116, rs2273061, rs2235811 and rs6040061), MEF2C (rs1366594, rs12521522 and rs11951031), and BDNF (rs6265) and the data using linear regression.
Results: The JAG1 SNP rs2235811 was associated with the BMD of the total body under the dominant inheritance model (p=0,024). Although the other SNPs were not associated with BMD in any of the inheritance models studied, a trend was observed.
Conclusion: Our results suggest that the SNP rs2235811 in the JAG1 gene might contribute to the variation in BMD in women from northern México.
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References
World Health Organization. Prevention and management of osteoporosis: Report of a WHO scientific group. Singapur: WHO; 2003. p. 921.
Muñoz-Torres M, Varsavsky M, Avilés-Pérez MD. Osteoporosis. Definición epidemiología. Rev Osteoporos Metab Miner. 2010;2(Supl.3):S5-7.
Clark P, Carlos F, Vázquez-Martínez LJ. Epidemiology, costs and burden of osteoporosis in México. Arch Osteoporos. 2010;5:9-17.
Özbaş H, Tutgun-Onrat S, Özdamar K. Genetic and environmental factors in human osteoporosis. Mol Biol Rep. 2012;39:11289-96. https://doi.org/10.1007/s11033-012-2038-5
Ng MYM, Sham PC, Paterson AD, Chan V, Kung AW. Effect of environmental factors and gender on the heritability of bone mineral density and bone size. Ann Hum Genet. 2006;70: 428-38. https://doi.org/10.1111/j.1469-1809.2005.00242.x
Estrada K, Styrkarsdottir U, Evangelos E, Hsu YH, Duncan EL, Ntzani EE, et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012;44:491-501. https://doi.org/10.1038/ng.2249
Rivadeneira F, Styrkársdottir U, Estrada K, Halldórsson BV, Hsu YH, Richards JB, et al. Twenty bone mineral density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet. 2009;41:1199-206. https://doi.org/10.1038/ng.446
Styrkarsdottir U, Halldorsson BV, Gudbjartsson DF, Tang NL, Koh JM, Xiao S, et al. European bone mineral density loci are also associated with BMD in East-Asian population. PLoS One. 2010;5:e13217. https://doi.org/10.1371/journal.pone.0013217
Lisker R, López MA, Jasqui S, Ponce de León Rosales, S, Correa-Rotter R, Sánchez S, et al. Association of vitamin D receptor polymorphisms with osteoporosis in Mexican postmenopausal women. Hum Biol. 2003;75:399-403. https://doi.org/10.1353/hub.2003.0045
González-Mercado A, Sánchez-López JY, Regla-Nava JA, Gámez-Nava JI, González-López L, Durán-González J, et al. Association analysis of vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal Mexican-Mestizo women. Genet Mol Res. 2013;12:2755-63. https://doi.org/10.4238/2013.July.30.13
Castelán-Martínez OD, Vivanco-Muñoz N, Falcón-Ramírez E, Valdés-Flores M, Clark P. Apa1 VDR polymorphism and osteoporosis risk in postmenopausal Mexican women. Gac Med Mex. 2015;151:472-6.
Jiménez-Salas Z, Hernández-Tobías EA, Ramírez-López TE, Campos-Góngora E. Association of polymorphism TaqI of vitamin D receptor with bone mineral density in young Mexican women. Nutr Hosp. 2012;27:1505-10. https://doi.org/10.3305/nh.2012.27.5.5673
Gómez R, Magaña JJ, Cisneros B, Pérez-Salazar E, Faugeron S, Véliz D, et al. Association of the estrogen receptor alpha gene polymorphisms with osteoporosis in the Mexican population. Clin Genet. 2007;72:574-81. https://doi.org/10.1111/j.1399-0004.2007.00898.x
Falcón-Ramírez E, Casas-Ávila L, Miranda A, Díez P, Castro C, Rubio J, et al. Sp1 polymorphism in collagen I α1 gene is associated with osteoporosis in lumbar spine of Mexican women. Mol Biol Rep. 2011;38:2987-92. https://doi.org/10.1007/s11033-010-9963-y
Magaña JJ, Gómez R, Cisneros B, Casas L, Valdés-Flores M. Association of interleukin-6 gene polymorphisms with bone mineral density in Mexican women. Arch Med Res. 2008;39:618-24. https://doi.org/10.1016/j.arcmed.2008.05.006
Magaña JJ, Gómez R, Cisneros B, Casas L, Castorena F, Miranda A, et al. Association of the CT gene (CA) polymorphism with BMD in osteoporotic Mexican women. Clin Genet. 2006;70:402-8. https://doi.org/10.1111/j.1399-0004.2006.00703.x
Falcón-Ramírez E, Casas-Ávila L, Cerda-Flores RM, Castro-Hernández C, Rubio-Lightbourn J, Velázquez-Cruz R, et al. Association of LRP5 haplotypes with osteoporosis in Mexican women. Mol Biol Rep. 2013;40:2705-10. https://doi.org/10.1007/s11033-012-2357-6
Villalobos-Comparán M, Jiménez-Ortega RF, Estrada K, Parra-Torres AY, González-Mercado A, Patiño N, et al. A pilot genome-wide association study in postmenopausal Mexican-Mestizo women implicates the RMND1/CCDC170 locus is associated with bone mineral density. Int J Genomics. 2017;2017:5831020. https://doi.org/10.1155/2017/5831020
Kramer I, Baertschi S, Halleux C, Keller H, Kneissel M. Mef2c deletion in osteocytes results in increased bone mass. J Bone Miner Res. 2012;27:360-73. https://doi.org/10.1002/jbmr.1492
Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ. Update on Wnt signaling in bone cell biology and bone disease. Gene. 2012;492:1-18. https://doi.org/10.1016/j.gene.2011.10.044
Gifre L, Ruiz-Gaspá S, Monegal A, Nomdedeu B, Filella X, Guañabens N, et al. Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone. 2013;57:272-6. https://doi.org/10.1016/j.bone.2013.08.016
Johnson ME, Deliard S, Zhu F, Xia Q, Wells AD, Hankenson KD, et al. A ChIP-seq-defined genome-wide map of MEF2C binding reveals inflammatory pathways associated with its role in bone density determination. Calcif Tissue Int. 2014;94:396-402. https://doi.org/10.1007/s00223-013-9824-5
Park SE, Oh KW, Lee WY, Baek KH, Yoon KH, Son HY, et al. Association of osteoporosis susceptibility genes with bone mineral density and bone metabolism related markers in Koreans: The Chungju Metabolic Disease Cohort (CMC) study. Endocr J. 2014;61:1069-78. https://doi.org/10.1507/endocrj.EJ14-0119
Zhu F, Sweetwyne MT, Hankenson KD. PKCδ is required for Jagged-1 induction of human mesenchymal stem cell osteogenic differentiation. Stem Cells. 2013;31:1181-92.
https://doi.org/10.1002/stem.1353
Kung AW, Xiao SM, Cherny S, Li GH, Gao Y, Tso G, et al. Association of JAG1 with bone mineral density and osteoporotic fractures: A genome-wide association study and follow-up replication studies. Am J Hum Genet. 2010;86:229-39. https://doi.org/10.1016/j.ahg.2009.12.014
Rojano-Mejía D, Coral-Vázquez RM, Cortés-Espinosa L, López-Medina G, Aguirre-García MC, Coronel A, et al. JAG1 and COL1A1 polymorphisms and haplotypes in relation to bone mineral density variations in postmenopausal Mexican-Mestizo women. Age (Dordr). 2013;35:471-8. https://doi.org/10.1007/s11357-011-9363-9
Velázquez-Cruz R, Jiménez-Ortega RF, Parra-Torres A, Castillejos-López M, Patiño N, Quiterio M, et al. Analysis of association of MEF2C, SOST and JAG1 genes with bone mineral density in Mexican-Mestizo postmenopausal women. BMC Musculoskelet Disord. 2014;15:400. https://doi.org/10.1186/1471-2474-15-400
McDowell KA, Hutchinson AN, Wong-Goodrich SJ, Presby MM, Su D, Rodríguez RM, et al. Reduced cortical BDNF expression and aberrant memory in Carf knock-out mice. J Neurosci. 2010;30:7453-65. https://doi.org/10.1523/JNEUROSCI.3997-09.2010
Nakanishi T, Takahashi K, Aoki C, Nishikawa K, Hattori T, Taniguchi S. Expression of nerve growth factor family neurotrophins in a mouse osteoblastic cell line. Biochem Biophys Res Commun. 1994;198:891-7. https://doi.org/10.1006/bbrc.1994.1127
Deng FY, Tan LJ, Shen H, Liu YJ, Liu YZ, Li J, et al. SNP rs6265 regulates protein phosphorylation and osteoblast differentiation and influences BMD in humans. J Bone Miner Res.2013;28:2498-507. https://doi.org/10.1002/jbmr.1997
Guo Y, Dong SS, Chen XF, Jing YA, Yang M, Yan H, et al. Integrating epigenomic elements and GWASs identifies BDNF gene affecting bone mineral density and osteoporotic fracture risk. Sci Rep. 2016;6:30558. https://doi.org/10.1038/srep30558
Price AL, Butler J, Patterson N, Capelli C, Pascali VL, Scarnicci F, et al. Discerning the ancestry of European Americans in genetic association studies. PLoS Genet. 2008;4:e236. https://doi.org/10.1371/journal.pgen.0030236
Silva-Zolezzi I, Hidalgo-Miranda A, Estrada-Gil J, Fernández-López JC, Uribe-Figueroa L, Contreras A, et al. Analysis of genomic diversity in Mexican Mestizo populations to develop genomic medicine in México. Proc Natl Acad Sci USA. 2009;106:8611-6. https://doi.org/10.1073/pnas.0903045106
Moreno-Estrada A, Gignoux CR, Fernández-López JC, Zakharia F, Sikora M, Contreras AV, et al. Human genetics. The genetics of México recapitulates Native American substructure and affects biomedical traits. Science. 2014;344:1280-5. https://doi.org/10.1126/science.1251688
Delezé M, Cons-Molina F, Villa AR, Morales-Torres J, González-González JG, Calva JJ, et al. Geographic differences in bone mineral density of Mexican women. Osteoporos Int. 2000;11:562-9.
Deng HW, Shen H, Xu FH, Deng HY, Conway T, Zhang HT, et al. Test of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. J Bone Miner Res. 2002;17:678-86. https://doi.org/10.1359/jbmr.2002.17.4.678
Secretaría de Salud. Reglamento de la Ley General de Salud en Materia de Investigación para la Salud. Fecha de consulta: 21 de marzo de 2016. Disponible en: http://www.salud.gob.mx/unidades/cdi/nom/compi/rlgsmis.html
Court MH. A simple calculator to determine whether observed genotype frequencies are consistent with Hardy-Weinberg equilibrium. (2005-2008). Comparative and Molecular Pharmacogenomics Laboratory, Tufts University. Fecha de consulta: 12 de marzo de 2016.Disponible en: http://fletcher.tufts.edu/~/media/Fletcher/Microsites/congratulations/AY2016-2017%20Certification%20of%20Souces%20of%20Funds%20Form.pdf
Iniesta R, Guinó E, Moreno V. Análisis estadístico de polimorfismos genéticos en estudios epidemiológicos. Gac Sanit. 2005;19:333-41.
Ensembl.org. Human (GRCh38.p10). Fecha de consulta: 12 de marzo de 2016. Disponible en: http://www.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=5:89079744-89080744;v=rs1366594;vdb=variation;vf=926764#population_freq_AMR
Kajiya M, Shiba H, Fujita T, Ouhara K, Takeda K, Mizuno N, et al. Brain-derived neurotrophic factor stimulates bone/cementum-related protein gene expression in cementoblasts. J Biol Chem. 2008;283:16259-67. https://doi.org/10.1074/jbc.M800668200
Contreras-Cubas C, Sánchez-Hernández BE, García-Ortiz H, Martínez-Hernández A, Barajas-Olmos F, Cid M, et al. Heterogenous distribution of MTHFR gene variants among Mestizos and diverse Amerindian groups from Mexico. PLoS One. 2016;11:e0163248. https://doi.org/10.1371/journal.pone.0163248
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