Association between the T538C Polymorphism in Bone Morphogenetic Protein 4 and the Risk of Non-syndromic Cleft Lip with or without Cleft Palate: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 LIULu-liang ,  GUOFu-lin , GuBo-yu

Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital, Harbin Medical University, Harbin 150001, China;

Corresponding author：

GUOFu-lin, Email: flguo1967@126.com

Keywords：

Bone morphogenetic protein 4; Non-syndromic cleft lip with or without cleft palate; Polymorphism; Meta-analysis; Systematic review; Case-control study

DOI：

10.7507/1672-2531.20150106

Video：

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Objective To systematically review the correlation between the T538C polymorphism in bone morphogenetic protein 4 (BMP-4) and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). Methods We electronically searched databases including PubMed, The Cochrane Library, EMbase, CBM, CNKI, VIP, and WanFang Data from inception to November 2014, to collect case-control studies of the correlation between the T538C polymorphism in BMP-4 and the risk of NSCL/P. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.2 software. Results A total of 6 case-control studies involving 926 cases and 1 110 controls were included. The results of meta-analysis showed that:there was no significant association between the T538C polymorphism in BMP-4 gene and the risk of NSCL/P (C vs. T:OR=1.14, 95% CI 0.78 to 1.66; CC vs. TT:OR=0.75, 95% CI 0.50 to 1.11; CC vs. TT:OR=1.53, 95% CI 0.69 to 3.37; CC vs. CT+TT:OR=1.80, 95% CI 0.96 to 3.38; CC+CT vs. TT:OR=0.90, 95% CI 0.57 to 1.43). Subgroup analysis based on ethnicity showed that, the T538C polymorphism in BMP-4 gene was associated with increased risk of NSCL/P in Asian population (C vs. T:OR=1.54, 95% CI 1.26 to 1.87; CC vs. TT:OR=2.91, 95% CI 1.88 to 4.52; CC vs. CT+TT:OR=2.99, 95% CI 1.99 to 4.49), but decreased risk of NSCL/P in Latin populations (C vs. T:OR=0.69, 95% CI 0.50 to 0.96; CT vs. TT:OR=0.52, 95% CI 0.40 to 0.68; CC+CT vs. TT:OR=0.52, 95% CI 0.35 to 0.78). Conclusion Available evidence suggests that the T538C polymorphism in BMP-4 gene may be associated with increased risk of NSCL/P in Asians and decreased risk of NSCL/P in Latinas. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

Citation： LIULu-liang, GUOFu-lin, GuBo-yu. Association between the T538C Polymorphism in Bone Morphogenetic Protein 4 and the Risk of Non-syndromic Cleft Lip with or without Cleft Palate: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(6): 633-638. doi: 10.7507/1672-2531.20150106 Copy

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11.	卢丹.山东地区非综合征性唇腭裂与MTHFR基因C677T和BMP-4基因T538C多态性的相关性研究.山东大学,2011.
12.	王慧,周小平,崔毓贵,等.BMP-4基因rs17563位点多态性与中国华东地区部分人群非综合征性唇腭裂的关系.江苏医药,2012,38(8):897-900.
13.	Araújo TK,Simioni M,Félix TM,et al.Preliminary analysis of the nonsynonymous polymorphism rs17563 in BMP-4 gene in Brazilian population suggests protection for nonsyndromic cleft lip and palate.Plast Surg Int,2012,2012:247104.
14.	Antunes LS,Küchler EC,Tannure PN,et al.BMP-4 Polymorphism is associated with nonsyndromic oral cleft in a Brazilian population.Cleft Palate Craniofac J,2013,50(6):633-638.
15.	由林,焦晓辉,张冰,等.中国北方人群非综合征性唇腭裂与BMP-4基因多态性的关系.北京口腔医学,2013,21(1):82-84.
16.	Wozney JM,Rosen V,Celeste AJ,et al.Novel regulators of bone formation:molecular clones and activities.Science,1988,242(4885):1528-1534.
17.	Foppiano S,Hu D,Marcucio RS.Signaling by bone morphogenetic proteins directs formation of an ectodermal signaling center that regulates craniofacial development.Dev Biol,2007,312(1):103-114.
18.	Juriloff DM,Harris MJ.Mouse genetic models of cleft lip with or without cleft palate.Birth Defects Res A Clin Mol Teratol,2008,82(2):63-77.
19.	Lin JY,Chen YJ,Huang YL,et al.Association of bone morphogenetic protein 4 gene polymorphisms with nonsyndromic cleft lip with or without cleft palate in Chinese children.DNA Cell Biol,2008,27(11):601-605.

1. Dai L,Zhu J,Mao M,et al.Time trends in oral clefts in Chinese newborns:data from the Chinese National Birth Defects Monitoring Network.Birth Defects Res A Clin Mol Teratol,2010,88(1):41-47.
2. Beaty TH,Ruczinski I,Murray JC,et al.Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate.Genet Epidemiol,2011,35(6):469-478.
3. Little J,Cardy A,Munger RG.Tobacco smoking and oral clefts:a meta-analysis.Bull World Health Organ,2004,82(3):213-218.
4. Leite IC,Koifman S.Oral clefts,consanguinity,parental tobacco and alcohol use:a case-control study in Rio de Janeiro,Brazil.Braz Oral Res,2009,23(1):31-37.
5. Jia ZL,Shi B,Chen CH,et al.Maternal malnutrition,environmental exposure during pregnancy and the risk of non-syndromic orofacial clefts.Oral Dis,2011,17(6):584-589.
6. Mostowska A,Hozyasz KK,Wojcicki P,et al.Association between genetic variants of reported candidate genes or regions and risk of cleft lip with or without cleft palate in the polish population.Birth Defects Res A Clin Mol Teratol,2010,88(7):538-545.
7. 陈尔军,陈仁吉,穆玥,等.叶酸代谢相关基因与非综合征性唇腭裂的关系.口腔医学研究,2011,27(3):209-213.
8. Lennon CJ,Birkeland AC,Nuñez JA,et al.Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations.Laryngoscope,2012,122(9):2082-2087.
9. Beaty TH,Taub MA,Scott AF,et al.Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study.Hum Genet,2013,132(7):771-781.
10. Jianyan L,Zeqiang G,Yongjuan C,et al.Analysis of interactions between genetic variants of BMP-4 and environmental factors with nonsyndromic cleft lip with or without cleft palate susceptibility.Int J Oral Maxillofac Surg,2010,39(1):50-56.
11. 卢丹.山东地区非综合征性唇腭裂与MTHFR基因C677T和BMP-4基因T538C多态性的相关性研究.山东大学,2011.
12. 王慧,周小平,崔毓贵,等.BMP-4基因rs17563位点多态性与中国华东地区部分人群非综合征性唇腭裂的关系.江苏医药,2012,38(8):897-900.
13. Araújo TK,Simioni M,Félix TM,et al.Preliminary analysis of the nonsynonymous polymorphism rs17563 in BMP-4 gene in Brazilian population suggests protection for nonsyndromic cleft lip and palate.Plast Surg Int,2012,2012:247104.
14. Antunes LS,Küchler EC,Tannure PN,et al.BMP-4 Polymorphism is associated with nonsyndromic oral cleft in a Brazilian population.Cleft Palate Craniofac J,2013,50(6):633-638.
15. 由林,焦晓辉,张冰,等.中国北方人群非综合征性唇腭裂与BMP-4基因多态性的关系.北京口腔医学,2013,21(1):82-84.
16. Wozney JM,Rosen V,Celeste AJ,et al.Novel regulators of bone formation:molecular clones and activities.Science,1988,242(4885):1528-1534.
17. Foppiano S,Hu D,Marcucio RS.Signaling by bone morphogenetic proteins directs formation of an ectodermal signaling center that regulates craniofacial development.Dev Biol,2007,312(1):103-114.
18. Juriloff DM,Harris MJ.Mouse genetic models of cleft lip with or without cleft palate.Birth Defects Res A Clin Mol Teratol,2008,82(2):63-77.
19. Lin JY,Chen YJ,Huang YL,et al.Association of bone morphogenetic protein 4 gene polymorphisms with nonsyndromic cleft lip with or without cleft palate in Chinese children.DNA Cell Biol,2008,27(11):601-605.

Chinese Journal of Evidence-Based Medicine

Association between the T538C Polymorphism in Bone Morphogenetic Protein 4 and the Risk of Non-syndromic Cleft Lip with or without Cleft Palate: A Meta-analysis

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