Skip to main content
Download PDF
  • Research article
  • Open access
  • Published:

Association between 20q12 rs13041247 polymorphism and risk of nonsyndromic cleft lip with or without cleft palate: a meta-analysis

BMC Oral Health volume 20, Article number: 39 (2020) Cite this article

Abstract

Background

Previous genome-wide association studies have identified a link between the rs13041247 single nucleotide polymorphisms (SNPs) in the chromosome 20q12 locus and the development of the congenital malformation known as nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present meta-analysis was therefore designed to formally assess the relationship between rs13041247 and NSCL/P.

Methods

We searched Embase, Web of Science, PubMed, the China National Knowledge Internet (CNKI), and the China Wanfang database in order to identify relevant published through 25 June 2019. This allowed us to identify 13 studies incorporating 4914 patients and 5981 controls for whom rs13041247 genotyping had been conducted, with STATA 12.0 then being used to conduct a meta-analysis of these pooled results. The I2 statistic was used to compare heterogeneity among studies.

Results

In total this analysis incorporated 13 case-control studies. No association between the rs13041247 polymorphism and NSCL/P risk was detected in individuals of Asian ethnicity (C vs T: OR = 0.847, 95% CI = 0.702–1.021; CC vs TT: OR = 0.725, 95% CI = 0.494–1.063; CC vs CT: OR = 0.837, 95% CI = 0.657–1.067; CT + TT vs CC: OR = 1.265, 95% CI = 0.951–1.684; CC + CT vs TT: OR = 0.805, 95% CI = 0.630–1.029) or Caucasian ethnicity (C vs T: OR = 0.936, 95% CI = 0.786–1.114; CC vs TT: OR = 0.988, 95% CI = 0.674–1.446; CC vs CT: OR = 1.197, 95% CI = 0.816–1.757; CT + TT vs CC: OR = 0.918, 95% CI = 0.639–1.318; CC + CT vs TT: OR = 0.855, 95% CI = 0.677–1.081). However, an overall analysis of all participants in these studies revealed the rs13041247 C allele, the CT genotype, and the CC + CT model to be linked to a reduced NSCL/P risk (C vs T: OR = 0.897, 95% CI: 0.723–1.114, P = 0.048; CT vs TT: OR = 0.839, 95% CI: 0.734–0.959, P = 0.01; CC + CT vs TT: OR = 0.824, 95% CI: 0.701–0.968, P = 0.019).

Conclusion

These results suggest that the rs13041247 SNP located at the 20q12 chromosomal locus is associated with NSCL/P risk in an overall pooled study population, although this association was not significant in East Asian or Caucasian populations.

Peer Review reports

Background

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a congenital birth defect that affects a relatively high percentage of individuals in a manner that is linked to ethnicity [1], with rates ranging from 1.423/1000 in Chinese populations [2] to 1/500 in American Indian and Asian populations [3].

Both environmental and genetic factors can regulate the development of NSCL/P, but the underlying mechanisms are not fully understood at present. Recent genome-wide association studies have revealed that polymorphisms in the genomic region encoding the v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) are strongly associated with the risk of NSCL/P [4]. In line with this finding, multiple NSCL/P-related variants that may be causative of this condition have been identified in the 20q11.2 region of the genome, which is proximal to the MAFB gene [5].

Research regarding the rs13041247 polymorphism within the 20q12 chromosomal locus has provided strong evidence for the relevance of this single nucleotide polymorphism (SNP) to NSCL/P incidence Indian, Brazilian, Mesoamerican, and Chinese populations [5,6,7,8]. However, results have been inconsistent in different study populations, potentially due to the differences in ethnicity between these patient cohorts.

In order to fully explore the role of the rs1304127 in NSCL/P, the present meta-analysis of previously published case-control studies was conducted. This approach was employed in order to attain additional statistical power, allowing for the thorough examination of the relationship between this SNP and this congenital malformation in different populations. The results of this study have the potential to guide genetic counseling efforts in families at risk of or affected by NSCL/P.

Methods

Articles selection

Embase, Web of Science, PubMed, the China National Knowledge Internet (CNKI) and the China Wanfang database were searched for articles published through 25 June 2019. Search terms used were as follows: (“nonsyndromic cleft lip with or without cleft palate” or “cleft palate” or “cleft lip” or “orofacial clefts” or “oral cleft” or “CL” or “CP” or “NSCL/P”) and (“MAFB” or “20q12” or “v-maf musculoaponeurotic fibrosarcoma oncogene homolog B”) and (“polymorphism” or “allele” or “gene” or “SNP”). No restrictions were imposed upon the language in which articles were published.

Study selection and data extraction

In order to be included in this meta-analysis, studies had to meet the following inclusion criteria: (1) Studies were case-control studies; (2) Studies were focused on NSCL/P; (3) Polymorphisms analyzed in the study included rs13041247 at the 20q12 locus; (4) Studies provided sufficient data necessary for the calculation of odds ratios (ORs) and 95% confidence intervals (CIs); (5) All necessary data was either available or was obtained within two attempts to contact the study authors. When multiple articles included overlapping patient cohorts, only the study with the most comprehensive information was included in the present meta-analysis (i.e. the study with the largest population or the most complete dataset). In addition, studies meeting the following criteria were excluded from this analysis: (1) Animals studies; (2) Reviews, letters, or abstracts lacking original data; (3) Case-reports; (4) Studies focused only on other SNPs or which lacked a control group. No language restrictions were imposed on these studies.

Two authors (Liheng Huang and Yangzhan Ou), independently reviewed identified studies in order to exclude those which were either clearly irrelevant or which were duplicates, after which a full text review was performed to identify studies meeting the inclusion criteria for this analysis. Any discrepancies were resolved via discussion with the third author (Yunpu He).The following pieces of data were extracted from these studies: Name of the first author, year of publication, country, population ethnicities, control source, study design, samples size, control Hardy-Weinberg equilibrium (HWE) p-values, genotyping methodology, and case/control genotype distributions (Table 1) [5,6,7,8,9,10,11,12,13,14,15,16,17]. In addition, the Newcastle-Ottawa scale was used by two authors (Yunpu He and Shijie Tang) to independently evaluate included study quality as recommended previously [18]. In total, 8 of the included studies reported on polymorphisms in Chinese and East Asian populations, 2 focused on Caucasian populations Germany and Brazil [15, 16], and 1 each focused on Nigerian [17], Brazilian [7], Mayan Mesoamerican [8], Indian [5] ethnic populations. For those subgroups for which more than one article was available, ethnicity-based subgroup analyses were performed.

Table 1 The basic information and data of 13 studies in the meta-analysis
Full size table

Statistical analysis

STATA 12.0 was used to obtain crude ORs and 95% CIs for each of the included articles as a means of assessing the relationship between the rs13041247 SNP and NSCL/P risk. Chi-squared tests were used to assess the HWE in the control group, revealing it not to differ significantly from HWE (P > 0.05). Ethnicity-based subgroup analyses were also conducted. Five different genetic models were used to examine the rs13041247 and NSCL/P risk according to ORs and 95% CIs: an allele model (C vs T), a homozygote model (CC vs TT), a heterozygote model (CC vs CT), a dominant model (CT + TT vs CC), and a recessive model (CC + CT vs TT). Z-tests were used to assess the significance of pooled ORs, P < 0.05 as the significance threshold. The I2 statistic was used to assess heterogeneity among studies, with I2 > 50% being consistent with significant heterogeneity, leading to the use of a random effect model, and I2 < 50% leading to the use of a fixed effect model. Sensitivity analyses were conducted by iteratively omitting individual studies from the overall analysis, while funnel plots were used to examine the risk of publication bias.

Results

Study characteristics

The study selection process for the present meta-analysis is detailed in Fig. 1, with the characteristics of included studies shown in Table 1. In total, 13 case-control studies were included in the present meta-analysis, incorporating a total of 4914 cases and 5981 controls in whom rs13041247 genotyping had been performed [5,6,7,8,9,10,11,12,13,14,15,16,17]. These studies included diverse populations from a range of ethnicities, including East Asian, Caucasian, India, Mayan, Brazilian, and African cohorts. The quality of these studies was assessed using the Newcastle-Ottawa scale (NOS), revealing all of these studies to be of high quality with scores > 7 out of a possible 9 (Table 2).

Fig. 1
figure 1

Flow diagram of study selection process

Full size image
Table 2 Quality assessment scores for the studies included in this meta-analysis
Full size table

Meta-analysis results

Table 3 highlights the results of this meta-analysis of the relationship between rs13041247 and NSCL/P risk. Ultimately, this analysis revealed no significant association between rs13041247 and NSCL/P risk in an East Asian population (C vs T: OR = 0.847, 95% CI = 0.702–1.021; CC vs TT: OR = 0.725, 95% CI = 0.494–1.063; CC vs CT: OR = 0.837, 95% CI = 0.657–1.067; CT + TT vs CC: OR = 1.265, 95% CI = 0.951–1.684; CC + CT vs TT: OR = 0.805, 95% CI = 0.630–1.029) or in a Caucasian population (C vs T: OR = 0.936, 95% CI = 0.786–1.114; CC vs TT: OR = 0.988, 95% CI = 0.674–1.446; CC vs CT: OR = 1.197, 95% CI = 0.816–1.757; CT + TT vs CC: OR = 0.918, 95% CI = 0.639–1.318; CC + CT vs TT: OR = 0.855, 95% CI = 0.677–1.081). However, when the overall combined patient/control populations were analyzed, this analysis revealed that the C allele, the CT genotype, and the CC + CT model to be associated with significantly reduced NSCL/P risk (C vs T: OR = 0.897, 95% CI: 0.723–1.114, P = 0.048; CT vs TT: OR = 0.839, 95% CI: 0.734–0.959, P = 0.01; CC + CT vs TT: OR = 0.824, 95% CI: 0.701–0.968, P = 0.019). Significantly heterogeneity was detected in all models for both the overall and Asian analysis groups (I2 > 50%), whereas the heterogeneity in the Caucasian subgroup analysis was not significant. The results of this meta-analysis of the relationship between rs13041247 and NSCL/P risk for the allele model (C vs T), the heterozygote model (CC vs CT), the homozygote model (CC vs TT), the recessive model (CC + CT vs TT), and the dominant model (CT + TT vs CC) are shown in Figs. 2, 3, and 4. No significant changes in the study outcomes were detected in a sensitivity analysis, and no evidence of publication bias was detected based upon Egger’s test (East Asian P = 0.253, Caucasian P = 0.239, and Overall population P = 0.124). Similarly, no funnel plot asymmetry was detected (Figs. 5 and 6 for East Asian and Overall, respectively).

Table 3 Summary results of the association between polymorphism and NSCL/P risk in the meta-analysis
Full size table
Fig. 2
figure 2

Forest plot of the association between rs13041247 and NSCL/P risk in East Asian ethnicity

Full size image
Fig. 3
figure 3

Forest plot of the association between rs13041247 and NSCL/P risk in Caucasian ethnicity

Full size image
Fig. 4
figure 4

Forest plot of the association between rs13041247 and NSCL/P risk in Overall population

Full size image
Fig. 5
figure 5

Funnel plot of the association between rs13041247 and NSCL/P risk in East Asian ethnicity

Full size image
Fig. 6
figure 6

Funnel plot of the association between rs13041247 and NSCL/P risk in Overall population

Full size image

Discussion

This meta-analysis incorporated 13 total articles examining the relationship between rs13041247 and NSCL/P risk, with data available for 4914 patients and 5981 controls. In a subgroup analysis of different ethnic groups, we observed no significant association between rs13041247 and NSCL/P risk. However, in an analysis of the overall study population we found the C allele, the CT genotype and the CC + CT model to be significantly linked with reduced NSCL/P risk (C vs T: OR = 0.897, 95% CI: 0.723–1.114, P = 0.048; CT vs TT: OR = 0.839, 95% CI: 0.734–0.959, P = 0.01; CC + CT vs TT: OR = 0.824, 95% CI: 0.701–0.968, P = 0.019). The molecular basis for NSCL/P remains poorly characterized, with both genetic and environmental factors being thought to drive the development of this disease. Risk factors such as maternal drinking, smoking, and poor nutrition prior to conception may influence this risk of this birth defect. Several meta-analyses have recently highlight a number of genetic and environmental risk factors associated with NSCL/P development [19,20,21,22,23,24,25,26].

The MAFB gene is a transcription factor with a basic leucine zipper structure encoded in the 20q12 region [27]. MAFB is a key regulator of the development of endocrine cells, hematopoietic cells, and the development of the orofacial region in addition to functioning in medullary contexts as a tumor suppressor gene [28,29,30]. Work by Beaty et al. revealed a strong association between NSCL/P risk and SNPs in the MAFB gene in an Asian population. The rs13041247 has been associated with reduced NSCL/P risk in certain studies, whereas others have failed to detect such an association in Caucasian, Brazilian, or Mexican Mestizo populations [7]. A recent meta-analysis by Imani et al. examined the link between the rs13041247 polymorphism and NSCL/P risk [20]. The results of our present analysis were partially consistent with this prior meta-analysis, which had included 10 total studies of Asian, Caucasian, Mixed, and African populations. Our results for the CT vs. TT heterozygote model and the CC + CT vs TT recessive model were similar to those in this previous meta-analysis, whereas our findings regarding the C allele and the CC genotype different from those in this prior study. We found that the C allele was related to NSCL/P risk, whereas the homozygote model was not. This analysis therefore reaffirmed and expanded upon this prior study, expanding the number of included studies to 13, thus yielding a larger sample size that produced some results inconsistent with those of the previous study.

The present meta-analysis has several limitations. For one, the sample size in this analysis was relatively small, limiting our ability to precisely assess the relationship between rs13041247 and NSCL/P risk. Secondly, these analyses were based upon one-way estimates. Furthermore, there was significantly heterogeneity among studies. In addition, we were unable to adjust for maternal risk factors such as alcohol intake or smoking as this information was unavailable in the majority of the included studies. Lastly, we were unable to assess gene-environment and gene-gene interactions for the same reason.

Conclusion

In summary, the present meta-analysis revealed that the rs13041247 SNP located in the 20q12 region is significantly linked to NSCL/P risk, which the C allele, the CT genotype and the CC + CT model for this SNP being associated with reduced NSCL/P risk in an overall study population. However, subgroup analyses in individual ethnic groups failed to detect any significant relationship between rs13041247 and NSCL/P risk. Future large-scale well-designed studies will therefore be essential to accurately assess the relationship between rs13041247 SNP and NSCL/P risk in order to better understand the etiology of this complex disorder.

Availability of data and materials

The datasets generated and analyzed during thte current study are available from the corresponding author on reasonable request.

Abbreviations

C vs T:

The allele model

CC vs CT:

The heterozygote model

CC vs TT:

The homozygote model

CC + CT vs TT:

The recessive model

CI:

Confidence interval

CL:

Cleft lip

CNKI:

The China National Knowledge Internet

CP:

Cleft palate

CT + TT vs CC:

The dominant model

F:

The fixed effect model

HWE:

Hardy-Weinberg equilibrium

I2 :

I-squared

MAFB:

V-maf musculoaponeurotic fibrosarcoma oncogene homolog B

NOS:

Newcastle-Ottawa scale

NSCL/P:

Nonsyndromic cleft lip with or without cleft palate

OR:

Odds ratio

R:

The random effect model

SNP:

Single nucleotide polymorphisms

References

  1. Bender PL. Genetics of cleft lip and palate. J Pediatr Nurs. 2000;15(4):242–9.

    Article  Google Scholar 

  2. Dai L, Zhu J, Mao M, Li Y, Deng Y, Wang Y, et al. Time trends in oral clefts in Chinese newborns: data from the Chinese National Birth Defects Monitoring Network. Birth defects research Part A, Clinical and molecular teratology. 2010;88(1):41–7.

    PubMed  PubMed Central  Google Scholar 

  3. Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet (London, England). 2009; 374(9703):1773–1785.

    Article  Google Scholar 

  4. Beaty TH, Murray JC, Marazita ML, Munger RG, Ruczinski I, Hetmanski JB, et al. A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat Genet. 2010;42(6):525–9.

    Article  Google Scholar 

  5. Gurramkonda VB, Syed AH, Murthy J, Chaubey G, Lakkakula VKSB. Polymorphic variants near 1p22 and 20q11.2 loci and the risk of non-syndromic cleft lip and palate in south Indian population. Int J Pediatr Otorhinolaryngol. 2015;79(12):2389–93.

    Article  Google Scholar 

  6. Yin X, Ma L, Li Y, Xu M, Wang W, Wang H, et al. Genetic variants of 20q12 contributed to non-syndromic orofacial clefts susceptibility. Oral Dis. 2017;23(1):50–4.

    Article  Google Scholar 

  7. do Rego Borges A, Sa J, Hoshi R, Viena CS, Mariano LC, de Castro Veiga P et al. Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Brazilian population with high African ancestry. American journal of medical genetics Part A. 2015; 167a(10):2344–2349.

  8. Ludwig KU, Wahle P, Reutter H, Paredes-Zenteno M, Muñoz-Jimenez SG, Ortiz-Lopez R, et al. Evaluating eight newly identified susceptibility loci for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population. Birth Defects Research Part A - Clinical and Molecular Teratology. 2014;100(1):43–7.

    Article  Google Scholar 

  9. Huang E, Cheng H, Xu M, Shu S, Tang S. Association between single-nucleotide polymorphisms on chromosome 1p22 and 20q12 and nonsyndromic cleft lip with or without cleft palate: new data in Han Chinese and meta-analysis. Birth Defects Research Part A - Clinical and Molecular Teratology. 2012;94(6):469–76.

    Article  Google Scholar 

  10. Feifei L, Hongke D, Yanbing C, Li D, Aihua Y. The association of MAFB rs13041247 polymorphism with nonsyndromic cleft lip with or without cleft palate in Guangdong population. Shandong Medical Journal. 2017;57(35):55–7.

    Google Scholar 

  11. Zhougwei Z, Lijuan M, Yongqing H, Min J, Jian M, Yanhua X, et al. Association of chromosome 8q24 and MAFB gene polymorphism with nonsyndromic cleft lip with or wtihout cleft palate in Ningixia populaiton. Journal of Chongqing Medical University. 2013;38(03):230–4.

    Google Scholar 

  12. Pan Y, Zhang W, Du Y, Tong N, Han Y, Zhang H, et al. Different roles of two novel susceptibility loci for nonsyndromic orofacial clefts in a Chinese Han population. Am J Med Genet A. 2011;155(9):2180–5.

    Article  Google Scholar 

  13. Mi N, Hao Y, Jiao X, Zheng X, Song T, Shi J, et al. Association study of single nucleotide polymorphisms of MAFB with non-syndromic cleft lip with or without cleft palate in a population in Heilongjiang Province, northern China. Br J Oral Maxillofac Surg. 2014;52(8):746–50.

    Article  Google Scholar 

  14. Sun Y, Huang Y, Yin A, Pan Y, Wang Y, Wang C, et al. Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate. Nat Commun. 2015;6.

  15. Reiter R, Brosch S, Goebel I, Ludwig KU, Pickhard A, Hoegel J, et al. A post GWAS association study of SNPs associated with cleft lip with or without cleft palate in submucous cleft palate. Am J Med Genet A. 2015;167(3):670–3.

    Article  Google Scholar 

  16. Fontoura C, Silva RM, Granjeiro JM, Letra A. Further evidence of association of the ABCA4 gene with cleft lip/palate. Eur J Oral Sci. 2012;120(6):553–7.

    Article  Google Scholar 

  17. Butali A, Mossey PA, Orth M, Adeyemo WL, Jezewski PA, Onwuamah CK, et al. Genetic studies in the Nigerian population implicate an MSX1 mutation in complex Oral facial Clefting disorders. Cleft Palate Craniofac J. 2011;48(6):646–53.

    Article  Google Scholar 

  18. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.

    Article  Google Scholar 

  19. Butali A, Little J, Chevrier C, Cordier S, Steegers-Theunissen R, Jugessur A, et al. Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: an individual participant data pooled-analysis. Birth defects research Part A, Clinical and molecular teratology. 2013;97(8):509–14.

    Article  Google Scholar 

  20. Imani MM, Lopez-Jornet P, Pons-Fuster Lopez E, Sadeghi M. Polymorphic Variants of V-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog B (rs13041247 and rs11696257) and Risk of Non-Syndromic Cleft Lip/Palate: Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2019; 16(15).

    Article  Google Scholar 

  21. Li YH, Yang J, Zhang JL, Liu JQ, Zheng Z, Hu DH. BMP4 rs17563 polymorphism and nonsyndromic cleft lip with or without cleft palate: a meta-analysis. Medicine. 2017;96(31):e7676.

    Article  Google Scholar 

  22. Wattanawong K, Rattanasiri S, McEvoy M, Attia J, Thakkinstian A. Association between IRF6 and 8q24 polymorphisms and nonsyndromic cleft lip with or without cleft palate: systematic review and meta-analysis. Birth defects research Part A, Clinical and molecular teratology. 2016;106(9):773–88.

    Article  Google Scholar 

  23. Xia Y, Hu B, Chen J, Zheng L, Song J. Association between the IRF6 rs2235371 polymorphism and the risk of nonsyndromic cleft lip with or without cleft palate in Chinese Han populations: a meta-analysis. Arch Oral Biol. 2017;84:161–8.

    Article  Google Scholar 

  24. Tang MR, Wang YX, Han SY, Guo S, Wang D. SUMO1 genetic polymorphisms may contribute to the risk of nonsyndromic cleft lip with or without palate: a meta-analysis. Genetic testing and molecular biomarkers. 2014;18(9):616–24.

    Article  Google Scholar 

  25. Pan Y, Zhang W, Ma J, Du Y, Li D, Cai Q et al. Infants' MTHFR polymorphisms and nonsyndromic orofacial clefts susceptibility: a meta-analysis based on 17 case-control studies. American journal of medical genetics Part A. 2012; 158a(9):2162–2169.

    Article  Google Scholar 

  26. Feng C, Zhang E, Duan W, Xu Z, Zhang Y, Lu L. Association between polymorphism of TGFA Taq I and cleft lip and/or palate: a meta-analysis. BMC oral health. 2014;14:88.

    Article  Google Scholar 

  27. Bakri Y, Sarrazin S, Mayer UP, Tillmanns S, Nerlov C, Boned A, et al. Balance of MafB and PU.1 specifies alternative macrophage or dendritic cell fate. Blood. 2005;105(7):2707–16.

    Article  Google Scholar 

  28. Tsuchiya M, Misaka R, Nitta K, Tsuchiya K. Transcriptional factors, Mafs and their biological roles. World J Diabetes. 2015;6(1):175–83.

    Article  Google Scholar 

  29. Suda N, Itoh T, Nakato R, Shirakawa D, Bando M, Katou Y et al. Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis. Development (Cambridge, England). 2014; 141(14):2885–2894.

    Article  Google Scholar 

  30. Gemelli C, Montanari M, Tenedini E, Zanocco Marani T, Vignudelli T, Siena M, et al. Virally mediated MafB transduction induces the monocyte commitment of human CD34+ hematopoietic stem/progenitor cells. Cell Death Differ. 2006;13(10):1686–96.

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank to Biji MJ language editing services for providing the editorial assistance.

Funding

This study was supported by the Medical Science and Technology Project of Shantou City of Guangdong Province, China (No. [2018]121), the National Natural Science Foundation of China (No. 81571920) and the Natural Science Foundation of Guangdong Province (No. 2015A030313436). The funding were not involved in the design of the study, the collection, analysis, and interpretation of data and in writing the manuscript. The funding was used as costs for English language editing service.

Author information

Author notes

  1. Liheng Huang and Xinglong Liang contributed equally to this work and should be considered cofirst authors.

Authors and Affiliations

  1. Department of Anesthesiology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, Guangdong, China

    Liheng Huang

  2. Department of Dermatology, Maoming People’s Hospital, Maoming, Guangdong, China

    Xinglong Liang

  3. Department of Plastic Surgery and Burn Center, the Second Affiliated Hospital, Shantou University Medical College, No.69 North Dong Xia Road, Shantou, 515041, Guangdong, China

    Yangzhan Ou, Shijie Tang & Yunpu He

Authors
  1. Liheng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinglong Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yangzhan Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shijie Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yunpu He
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YPH participated in selecting the meta-analysis study, extracting the data, performing the statistical analysis and drafting the manuscript. LHH, YZO, XLL and SJT participated in study selection, data extraction and manuscript drafting. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Shijie Tang or Yunpu He.

Ethics declarations

Ethics approval and consent to participate

This meta-analysis is conducted by the data from previously published papers, ethical approval and patient consent are not required.

Consent for publication

Not applicable.

Competing interests

All the authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, L., Liang, X., Ou, Y. et al. Association between 20q12 rs13041247 polymorphism and risk of nonsyndromic cleft lip with or without cleft palate: a meta-analysis. BMC Oral Health 20, 39 (2020). https://doi.org/10.1186/s12903-020-1003-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12903-020-1003-2

Keywords

BMC Oral Health

ISSN: 1472-6831

Contact us