Association between the methylenetetrahydrofolate reductase c.677C>T polymorphism and bone mineral density: an updated meta-analysis

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• 作者：Hong-Zhuo Li ; Wei Wang ; Yi-Ling Liu ; Xiao-Feng He
• 关键词：MTHFR ; Polymorphism ; BMD ; Susceptibility ; Meta ; analysis
• 刊名：Molecular Genetics and Genomics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：291
• 期：1
• 页码：169-180
• 全文大小：501 KB
• 参考文献：Abrahamsen B, Madsen JS, Tofteng CL, Stilgren L, Bladbjerg EM, Kristensen SR, Brixen K, Mosekilde L (2003) A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study. J Bone Miner Res 18:723–729PubMed CrossRef
  Abrahamsen B, Jørgensen HL, Nielsen TL, Andersen M, Haug E, Schwarz P, Hagen C, Brixen K (2006) MTHFR c.677C>T polymorphism as an independent predict or of peak bone mass in Danish men—results from the Odense Androgen Study. Bone 38:215–219PubMed CrossRef
  Agueda L, Urreizti R, Bustamante M, Jurado S, Garcia-Giralt N, Díez-Pérez A, Nogués X, Mellibovsky L, Grinberg D, Balcells S (2010) Analysis of three functional polymorphisms in relation to osteoporosis phenotypes: replication in a Spanish cohort. Calcif Tissue Int 87:14–24PubMed CrossRef
  Bagley PJ, Selhub J (1998) A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc Natl Acad Sci USA 95:13217–13220PubMed PubMedCentral CrossRef
  Brambila-Tapia AJ, Durán-González J, Sandoval-Ramírez L, Mena JP, Salazar-Páramo M, Gámez-Nava JI, González-López L, Lazalde-Medina BB, Dávalos NO, Peralta-Leal V, Vázquez del Mercado M, Beltrán-Miranda CP, Dávalos IP (2012) MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. Dis Markers 32:109–114PubMed PubMedCentral CrossRef
  Consensus Development Conference (1993) Diagnosis prophylactics and treatment of osteoporosis. Am J Med 94:646–650CrossRef
  Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TM (1993) Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet 341:962–963CrossRef
  DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMed CrossRef
  Devoto M, Specchia C, Li HH, Caminis J, Tenenhouse A, Rodriguez H, Spotila LD (2001) Variance component linkage analysis indicates a QTL for femoral neck bone mineral density on chromosome 1p36. Hum Mol Genet 10:2447–2452PubMed CrossRef
  Egger M, Smith DG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. Br Med J 315:629–634CrossRef
  Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113PubMed CrossRef
  Golbahar J, Hamidi A, Aminzadeh MA, Omrani GR (2004) Association of plasma folate, plasma total homocysteine, but not methylenetetrahydrofolate reductase C667T polymorphism, with bone mineral density in postmenopausal Iranian women: a cross-sectional study. Bone 35:760–765PubMed CrossRef
  Hak AE, Polderman KH, Westendorp IC, Jakobs C, Hofman A, Witteman JC, Stehouwer CD (2000) Increased plasma homocysteine after menopause. Atherosclerosis 149:163–168PubMed CrossRef
  Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analysis. Br Med J 327:557–560CrossRef
  Hong X, Hsu YH, Terwedow H, Tang G, Liu X, Jiang S, Xu X, Xu X (2007) Association of the methylenetetrahydrofolate reductase C677T polymorphism and fracture risk in Chinese postmenopausal women. Bone 40:737–742PubMed PubMedCentral CrossRef
  Kang SS, Wong PW, Zhou JM, Sora J, Lessick M, Ruggie N, Grcevich G (1988) Thermolabile methylenetetrahydrofolate reductase in patients with coronary artery disease. Metabolism 37:611–613PubMed CrossRef
  Kiel DP, Demissie S, Dupuis J, Lunetta KL, Murabito JM, Karasik D (2007) Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 8:S14PubMed PubMedCentral CrossRef
  Li M, Lau EM, Woo J (2004) Methylenetetrahydrofolate reductase polymorphism (MTHFR C677T) and bone mineral density in Chinese men and women. Bone 35:1369–1374PubMed CrossRef
  Macdonald HM, McGuigan FE, Fraser WD, New SA, Ralston SH, Reid DM (2004) Methylenetetrahydrofolate reductase polymorphism interacts with riboflavin intake to influence bone mineral density. Bone 35:957–964PubMed CrossRef
  Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. Natl Cancer Inst 22:719–748
  McLean RR, Karasik D, Selhub J, Tucker KL, Ordovas JM, Russo GT, Cupples LA, Jacques PF, Kiel DP (2004) Association of a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene with bone phenotypes depends on plasma folate status. J Bone Miner Res 19:410–418PubMed CrossRef
  Miyao M, Morita H, Hosoi T, Kurihara H, Inoue S, Hoshino S, Shiraki M, Yazaki Y, Ouchi Y (2000) Association of methylenetetrahydrofolate reductase (MTHFR) polymorphism with bone mineral density in postmenopausal Japanese women. Calcif Tissue Int 66:190–194PubMed CrossRef
  NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795CrossRef
  Nissen N, Madsen JS, Bladbjerg EM, Beck Jensen JE, Jørgensen NR, Langdahl B, Abrahamsen B, Brixen K (2009) No association between hip geometry and four common polymorphisms associated with fracture: the Danish osteoporosis prevention study. Calcif Tissue Int 84:276–285PubMed CrossRef
  Oishi Y, Watanabe Y, Shinoda S, Naka M, Ozawa Y, Matsuyama T, Morozumi K, Fuke Y (2012) The IL6 gene polymorphism -634C>G and IL17F gene polymorphism 7488T>C influence bone mineral density in young and elderly Japanese women. Gene 504:75–83PubMed CrossRef
  Pan Z, Trikalinos TA, Kavvoura FK, Lau J, Ioannidis JP (2005) Local literature bias in genetic epidemiology: an empirical evaluation of the Chinese literature. PLoS Med 2:e334PubMed PubMedCentral CrossRef
  Pandey SK, Singh A, Polipalli SK, Gupta S, Kapoor S (2013) Association of Methylene Tetrahydrofolate Reductase Polymorphism with BMD and Homocysteine in premenopausal North Indian Women. J Clin Diagn Res 7:2908–2911PubMed PubMedCentral
  Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberl S (1987) Genetic determinants of bone mass in adults: A twin study. J Clin Invest 80:706–710PubMed PubMedCentral CrossRef
  Ralston SH (2002) Genetic control of susceptibility to osteoporosis. J Clin Endocrinol Metab 87:2460–2466PubMed CrossRef
  Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofman A, Pols HA, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TD (2008) Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 371:1505–1512PubMed PubMedCentral CrossRef
  Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Richards JB, Zillikens MC, Kavvoura FK, Amin N, Aulchenko YS, Cupples LA, Deloukas P, Demissie S, Grundberg E, Hofman A, Kong A, Karasik D, van Meurs JB, Oostra B, Pastinen T, Pols HA, Sigurdsson G, Soranzo N, Thorleifsson G, Thorsteinsdottir U, Williams FM, Wilson SG, Zhou Y, Ralston SH, van Duijn CM, Spector T, Kiel DP, Stefansson K, Ioannidis JP, Uitterlinden AG (2009) Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet 41:1199–1206PubMed PubMedCentral CrossRef
  Shin MH, Choi JS, Rhee JA, Lee YH, Nam HS, Jeong SK, Park KS, Kim HY, Ryu SY, Choi SW, Song HR, Kim HN, Cauley JA, Kweon SS (2013) Association between methylenetetrahydrofolate reductase C677T polymorphism and bone mineral density: the Dong-gu Study and the Namwon Study. J Korean Med Sci 28:965–968PubMed PubMedCentral CrossRef
  Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Center JR, Nguyen TV, Bagger Y, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K (2008) Multiple genetic loci for bone mineral density and fractures. N Engl J Med 358:2355–2365PubMed CrossRef
  Tongboonchoo C, Tungtrongchitr A, Phonrat B, Preutthipan S, Tungtrongchitr R (2013) Association of MTHFR C677T polymorphism with bone mineral density of osteoporosis in postmenopausal Thai women. J Med Assoc Thai 96:133–139PubMed
  Villadsen MM, Bünger MH, Carstens M, Stenkjaer L, Langdahl BL (2005) Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with osteoporotic vertebral fractures, but is a weak predictor of BMD. Osteoporos Int 16:411–416PubMed CrossRef
  Wang H, Liu C (2012) Association of MTHFR C667T polymorphism with bone mineral density and fracture risk: an updated meta-analysis. Osteoporos Int 23:2625–2634PubMed CrossRef
  Yazdanpanah N, Uitterlinden AG, Zillikens MC, Jhamai M, Rivadeneira F, Hofman A, de Jonge R, Lindemans J, Pols HA, van Meurs JB (2008) Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele. J Bone Miner Res 23:86–94PubMed CrossRef
  Zhu K, Beilby J, Dick IM, Devine A, SoósM Prince RL (2009) The effects of homocysteine and MTHFR genotype on hip bone loss and fracture risk in elderly women. Osteoporos Int 20:1183–1191PubMed CrossRef
  
• 作者单位：Hong-Zhuo Li (1)
  Wei Wang (2)
  Yi-Ling Liu (3)
  Xiao-Feng He (4)
  
  1. Department of Orthopaedic, Peace Hospital of Changzhi Medical College, Changzhi, 046000, China
  2. Department of Gastroenterology, The Second People’s Hospital of Zhuhai, Zhuhai, 519000, China
  3. Department of Blood Transfusion, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
  4. Department of Research, Peace Hospital of Changzhi Medical College, Changzhi, 046000, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Biochemistry
  Microbial Genetics and Genomics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1617-4623

文摘

Many studies have reported an association between the methylenetetrahydrofolate reductase (MTHFR) c.677C>T polymorphism and reduced bone mineral density (BMD), but results have been inconsistent. We, therefore, performed a meta-analysis to further explore this association. Twenty-one studies, comprising 33,045 subjects, analyzed the association of MTHFR c.677C>T with femoral neck BMD. Significant association with reduced BMD was observed in Caucasians (recessive model: WMD = −0.004 g/cm2, 95 % CI −0.008 to −0.006), post-menopausal women (recessive model: WMD = −0.005 g/cm2, 95 % CI −0.007 to −0.003), men (dominant model: WMD = −0.004 g/cm2, 95 % CI −0.005 to −0.004; recessive model: WMD = −0.004 g/cm2, 95 % CI −0.005 to −0.004; TT vs. CC: WMD = −0.006 g/cm2, 95 % CI −0.006 to −0.006; CT vs. CC: WMD = −0.003 g/cm2, 95 % CI −0.003 to −0.003), and cohort studies (recessive model: WMD = −0.003 g/cm2, 95 % CI −0.006 to −0.001). Twenty-two studies, which included 32,271 subjects, analyzed the MTHFR c.677C>T association with lumbar spine BMD. Significant association with reduced BMD was observed in Caucasians, women, post-menopausal women, men, and cohort studies. Seven studies, comprising 6806 subjects, analyzed the MTHFR c.677C>T association with total hip BMD, but no significant association was observed in any population. Nine studies involving 5591 subjects analyzed the association with total body BMD. Significant association with reduced BMD was observed in overall and women subgroup analyses. In summary, this meta-analysis indicates that the MTHFR c.677C>T polymorphism is associated with reduced BMD in lumbar spine and femoral neck in Caucasians, post-menopausal women, and men, and with total body BMD in women. In addition, our results suggest that new studies examining the association between MTHFR c.677C>T polymorphism and BMD of lumbar spine and femoral neck in Asians is warranted, because I 2 > 75.0 % was observed. Keywords MTHFR Polymorphism BMD Susceptibility Meta-analysis