IRF6 Polymorphisms in Brazilian Patients with Non-syndromic Cleft Lip with or Without Palate

Overview

Journal Braz J Otorhinolaryngol

Specialty Otorhinolaryngology

Date 2019 Sep 10

PMID 31495697

Citations 3

Authors

Joao Felipe Bezerra

Heglayne Pereira Vital da Silva

Raul Hernandes Bortolin

Andre Ducati Luchessi

Marcela Abbott Galvao Ururahy

Melina Bezerra Loureiro

Vera Lucia Gil-da-Silva-Lopes

Maria das Gracas Almeida

Viviane Souza do Amaral

Adriana Augusto de Rezende

Affiliations

Soon will be listed here.

Abstract

Introduction: Non-syndromic orofacial clefts have a complex etiology due to the contribution from both genetic and environmental risk factors, as well as the interaction between them. Among the more than 15 susceptibility loci for non-syndromic orofacial clefts with considerable statistical and biological support, the IRF6 is the most validated gene by the majority of studies. Nonetheless, in genetically heterogeneous populations such as Brazilian, the confirmation of association between non-syndromic orofacial clefts and IRF6 common variants is not a consolidated fact and unrecognized IRF6 variants are poorly investigated.

Objective: The aim of this study was to investigate the association of IRF6 polymorphisms with non-syndromic orofacial clefts development in a population from northeast Brazil.

Methods: Blood samples of 186 non-syndromic orofacial clefts patients and 182 controls from Rio Grande do Norte, Brazil, were obtained to analyze IRF6 polymorphisms (rs2235371, rs642961, rs2236907, rs861019, and rs1044516) by real-time polymerase chain reaction. Non-syndromic orofacial clefts patients were classified in cleft lip and palate, cleft palate only and cleft lip only groups.

Results: The genotype and allele frequencies of single nucleotide polymorphism rs2235371 in IRF6 showed significant differences in patients with cleft palate when compared to the controls, whereas no association was shown between rs642961, rs2236907, rs861019, and rs1044516 and non-syndromic orofacial clefts.

Conclusion: The association found between rs2235371 and isolated cleft palate should be interpreted with caution due to the low number of individuals investigated, and more studies with larger sample size are needed to confirm these association. In addition, there is a lack of association of the rs642961, rs2236907 and rs861019 polymorphisms with non-syndromic orofacial clefts susceptibility.

Citing Articles

Sociodemographic Factors Associated with Knowledge About Management of Cleft Lip and Palate Patients in Peruvian Dental Students: A Logistic Regression Analysis.

Luyo-Penafiel B, Briceno-Vergel G, Ladera-Castaneda M, Cordova-Limaylla N, Huamani-Echaccaya J, Romero-Velasquez L Adv Med Educ Pract. 2023; 14:1287-1298.

PMID: 38028374 PMC: 10660724. DOI: 10.2147/AMEP.S437637.

Association of rs2013162 and rs2235375 Polymorphisms in Gene with Susceptibility to Non-Syndromic Cleft Lip and Palate.

Soleymani M, Ebadifar A, Khosravi M, Esmaeilzadeh E, Khorshid H Avicenna J Med Biotechnol. 2022; 14(2):181-185.

PMID: 35633982 PMC: 9077657. DOI: 10.18502/ajmb.v14i2.8885.

Non-syndromic Cleft Palate: An Overview on Human Genetic and Environmental Risk Factors.

Martinelli M, Palmieri A, Carinci F, Scapoli L Front Cell Dev Biol. 2020; 8:592271.

PMID: 33195260 PMC: 7606870. DOI: 10.3389/fcell.2020.592271.

References

Kondo S, Schutte B, Richardson R, Bjork B, Knight A, Watanabe Y . Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet. 2002; 32(2):285-9. PMC: 3169431. DOI: 10.1038/ng985. View

Wu T, Liang K, Hetmanski J, Ruczinski I, Fallin M, Ingersoll R . Evidence of gene-environment interaction for the IRF6 gene and maternal multivitamin supplementation in controlling the risk of cleft lip with/without cleft palate. Hum Genet. 2010; 128(4):401-10. PMC: 2956506. DOI: 10.1007/s00439-010-0863-y. View

Ingraham C, Kinoshita A, Kondo S, Yang B, Sajan S, Trout K . Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet. 2006; 38(11):1335-40. PMC: 2082114. DOI: 10.1038/ng1903. View

Pegelow M, Koillinen H, Magnusson M, Fransson I, Unneberg P, Kere J . Association and Mutation Analyses of the IRF6 Gene in Families With Nonsyndromic and Syndromic Cleft Lip and/or Cleft Palate. Cleft Palate Craniofac J. 2013; 51(1):49-55. DOI: 10.1597/11-220. View

Gabriel S, Schaffner S, Nguyen H, Moore J, Roy J, Blumenstiel B . The structure of haplotype blocks in the human genome. Science. 2002; 296(5576):2225-9. DOI: 10.1126/science.1069424. View

Paranaiba L, Bufalino A, Martelli-Junior H, de Barros L, Graner E, Coletta R . Lack of association between IRF6 polymorphisms (rs2235371 and rs642961) and non-syndromic cleft lip and/or palate in a Brazilian population. Oral Dis. 2009; 16(2):193-7. DOI: 10.1111/j.1601-0825.2009.01627.x. View

Park J, McIntosh I, Hetmanski J, Jabs E, Vander Kolk C, Wu-Chou Y . Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations. Genet Med. 2007; 9(4):219-27. PMC: 2846512. DOI: 10.1097/gim.0b013e3180423cca. View

Mai C, Cassell C, Meyer R, Isenburg J, Canfield M, Rickard R . Birth defects data from population-based birth defects surveillance programs in the United States, 2007 to 2011: highlighting orofacial clefts. Birth Defects Res A Clin Mol Teratol. 2014; 100(11):895-904. PMC: 4631395. DOI: 10.1002/bdra.23329. View

Zucchero T, Cooper M, Maher B, Daack-Hirsch S, Nepomuceno B, Ribeiro L . Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate. N Engl J Med. 2004; 351(8):769-80. DOI: 10.1056/NEJMoa032909. View

10.

Rahimov F, Marazita M, Visel A, Cooper M, Hitchler M, Rubini M . Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. Nat Genet. 2008; 40(11):1341-7. PMC: 2691688. DOI: 10.1038/ng.242. View

11.

Sivertsen A, Wilcox A, Skjaerven R, Vindenes H, Abyholm F, Harville E . Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives. BMJ. 2008; 336(7641):432-4. PMC: 2249683. DOI: 10.1136/bmj.39458.563611.AE. View

12.

Brito L, Bassi C, Masotti C, Malcher C, Rocha K, Schlesinger D . IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population. Am J Med Genet A. 2012; 158A(9):2170-5. DOI: 10.1002/ajmg.a.35526. View

13.

Shi J, Song T, Jiao X, Qin C, Zhou J . Single-nucleotide polymorphisms (SNPs) of the IRF6 and TFAP2A in non-syndromic cleft lip with or without cleft palate (NSCLP) in a northern Chinese population. Biochem Biophys Res Commun. 2011; 410(4):732-6. DOI: 10.1016/j.bbrc.2011.06.006. View

14.

Letra A, Fakhouri W, Fonseca R, Menezes R, Kempa I, Prasad J . Interaction between IRF6 and TGFA genes contribute to the risk of nonsyndromic cleft lip/palate. PLoS One. 2012; 7(9):e45441. PMC: 3447924. DOI: 10.1371/journal.pone.0045441. View

15.

Sun Y, Huang Y, Yin A, Pan Y, Wang Y, Wang C . 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. View

16.

Kerameddin S, Namipashaki A, Ebrahimi S, Ansari-Pour N . IRF6 Is a Marker of Severity in Nonsyndromic Cleft Lip/Palate. J Dent Res. 2015; 94(9 Suppl):226S-32S. DOI: 10.1177/0022034515581013. View

17.

Massenburg B, Jenny H, Saluja S, Meara J, Shrime M, Alonso N . Barriers to Cleft Lip and Palate Repair Around the World. J Craniofac Surg. 2016; 27(7):1741-1745. DOI: 10.1097/SCS.0000000000003038. View

18.

Watkins S, Meyer R, Strauss R, Aylsworth A . Classification, epidemiology, and genetics of orofacial clefts. Clin Plast Surg. 2014; 41(2):149-63. DOI: 10.1016/j.cps.2013.12.003. View

19.

Grosen D, Chevrier C, Skytthe A, Bille C, Molsted K, Sivertsen A . A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance. J Med Genet. 2009; 47(3):162-8. PMC: 2909851. DOI: 10.1136/jmg.2009.069385. View

20.

Khandelwal K, van Bokhoven H, Roscioli T, Carels C, Zhou H . Genomic approaches for studying craniofacial disorders. Am J Med Genet C Semin Med Genet. 2013; 163C(4):218-31. DOI: 10.1002/ajmg.c.31379. View