Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 8, August, p. 1109–1116

doi: 10.17219/acem/74388

Publication type: original article

Language: English

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Family-based study of association between MAFB gene polymorphisms and NSCL/P among Western Han Chinese population

Bihe Zhang1,B,D, Shijun Duan1,A,B,C,D,E,F, Jiayu Shi2,B,C, Shuyuan Jiang1,B,C, Fan Feng3,B,C, Bing Shi1,A,E, Zhonglin Jia1,A,C,E,F

1 State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, China

2 Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, USA

3 Air Force Dujiangyan Aviation Medicine Evaluation and Training Center, Chengdu, China

Abstract

Background. Non-syndromic cleft lip with or without cleft palate (NSCL/P) are the most common human congenital birth defects with a complex etiology. MAFB has been reported as a candidate gene involved in the pathogenesis of NSCL/P from genome-wide association study (GWAS) findings, and no replication studies have been performed in Western Han Chinese.
Objectives. The aim of this study was to investigate the associations of MAFB among NSCL/P trios in Western Han Chinese.
Material and Methods. We selected 6 single nucleotide polymorphisms (SNPs) (rs6072081, rs6065259, rs17820943, rs13041247, rs11698025 and rs6102085) near MAFB based on previous GWAS findings and recruited 298 case-parents trios with NSCL/P from Western Han Chinese population, while genotypes were done by SNPscan technology.
Results. Strong evidence of an association was found at rs17820943 (p = 0.0023; odds ratio – ORtranmission = 0.7 and 95% confidence interval [CI]: 0.55–0.88) and rs13041247 (p = 0.0023; ORtranmission = 0.7 and 95% CI: 0.55–0.88) among NSCL/P; genotypic transmission-disequilibrium test (TDT) analysis further confirmed this. C/C homozygote at rs17820943 (z = 3.44 and p = 0.00058) and T/T homozygote at rs13041247 (z = 3.14 and p = 0.0017) was over-transmitted among NSCL/P, which indicated they could increase the risk of having an affected baby. Sliding window haplotype analysis showed that haplotypes consisting of C allele at rs17820943 and T allele at rs13041247 were still over-transmitted among NSCL/P (lowest p = 0.0021).
Conclusion. This study further confirmed that the targeted SNPs at MAFB were associated with NSCL/P trios from Western Han Chinese population, which provides more scientific evidence for the future research and genetic counseling.

Key words

single nucleotide polymorphism, transmission disequilibrium test, MAFB, haplotype analysis, non-syndromic cleft lip with or without cleft palate

References (28)

  1. Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet. 2009;374:1773–1785.
  2. Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: Understanding genetic and environmental influences. Nat Rev Genet. 2011;12:167–178.
  3. 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;88:41–47.
  4. Harville EW, Wilcox AJ, Lie RT, Vindenes H, Åbyholm F. Cleft lip and palate versus cleft lip only: Are they distinct defects? Am J Epidemiol. 2005;162:448–453.
  5. Rahimov F, Marazita ML, Visel A, et al. Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. Nat Genet. 2008;40:1341–1347.
  6. Murray JC. Gene/environment causes of cleft lip and/or palate. Clin Genet. 2002;61:248–256.
  7. Xu H, Mathew G, George V. Family-based genome-wide association study for simulated data of Framingham Heart Study. BMC Proc. 2009;3(Suppl 7):S124–S128.
  8. Leslie EJ, Taub MA, Liu H, et al. Identification of functional variants for cleft lip with or without cleft palate in or near PAX7, FGFR2 and NOG by targeted sequencing of GWAS Loci. Am J Hum Genet. 2015;96:397–411.
  9. Birnbaum S, Ludwig KU, Reutter H, et al. Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24. Nat Genet. 2009;41:473–477.
  10. Grant SA, Wang K, Zhang H, et al. A genome-wide association study identifies a locus for nonsyndromic cleft lip with or without cleft palate on 8q24. J Pediatr. 2009;155:909–913.
  11. Mangold E, Ludwig KU, Birnbaum S, et al. Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate. Nat Genet. 2009;42:24–26.
  12. Beaty TH, Murray JC, Marazita ML, 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;42:525–529.
  13. Ludwig KU, Mangold E, Herms S, et al. Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. Nat Genet. 2012;44:968–971.
  14. Sun Y, Huang Y, Yin A, et al. Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate. Nat Commun. 2015;6:6414:doi:10.1038/ncomms7414
  15. Leslie EJ, Carlson JC, Shaffer JR, et al. A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13. Hum Mol Genet. 2016;25(13):2862–2872.
  16. Marchini J, Cardon LR, Phillips MS, Donnelly P. The effects of human population structure on large genetic association studies. Nat Genet. 2004;36:512–517.
  17. Li Q, Kim Y, Suktitipat B, et al. Gene-gene interaction among WNT genes for oral cleft in trios. Genet Epidemiol. 2015;39:385–394.
  18. Xu H, Shete S. Effects of population structure on genetic association studies. BMC Genet. 2005;6(Suppl 1):S109–S113.
  19. Yang Y, Cvekl A. Large Maf transcription factors: Cousins of AP-1 proteins and important regulators of cellular differentiation. Einstein J Biol Med. 2007;23:2–11.
  20. Pan Y, Zhang W, Du Y, et al. Different roles of two novel susceptibility loci for nonsyndromic orofacial clefts in a Chinese Han population. Am J Med Genet A. 2011;155A:2180–2185.
  21. Yuan QP, Blanton SH, Hecht JT. Association of ABCA4 and MAFB with non-syndromic cleft lip with or without cleft palate. Am J Med Genet A. 2011;155A:1469–1471.
  22. Lennon CJ, Birkeland AC, Nuňez JA, et al. Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations. Laryngoscope. 2012;122:2082–2087.
  23. 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: 553–557.
  24. Mi N, Hao Y, Jiao X, 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;52:746–750.
  25. Yin X, Ma L, Li Y, et al. Genetic variants of 20q12 contributed to non-syndromic orofacial clefts susceptibility. Oral Dis. 2017;23(1):50–54.
  26. Duan SJ, Huang N, Zhang BH, et al. New insights from GWAS for the cleft palate among han Chinese population. Med Oral Patol Oral Cir Bucal. 2017;22(2):e219–e227.
  27. Yu Q, He S, Zeng N, et al. BMP7 Gene involved in nonsyndromic orofacial clefts in Western Han Chinese. Med Oral Patol Oral Cir Bucal. 2015;20:e298–304.
  28. Rowlatt A, Hernández-Suárez G, Sanabria-Salas MC, et al. The heritability and patterns of DNA methylation in normal human colorectum. Hum Mol Genet. 2016;25(12):2600–2611.
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