Association between IRF6 rs642961 Polymorphism and Nonsyndromic Cleft Lip with or without Cleft Palate Risk in an Iranian Population

Authors

1 Department of Surgery, Division of Plastic and Reconstructive Surgery, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Department of Surgery, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Department of Oral and Maxillofacial Medicine, Dental School, Ardabil University of Medical Sciences, Ardabil, Iran

4 Department of Endodontic, Arak University of Medical Sciences, Arak, Iran

5 Pediatric Dentistry, Dental School, Arak University of Medical Sciences, Arak, Iran

6 Departments of Restorative and Esthetic, Arak University of Medical Sciences, Arak, Iran

7 Department of Medical Genetics, Kashan University of Medical Sciences, Kashan, Iran

8 Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Abstract

Background: The extent of the contribution of rs642961 polymorphism of interferon regulatory factor-6 (IRF6) gene with susceptibility to the syndromic cleft lip with or without cleft palate (NSCL/P) in the Iranian patients is still unknown. Thus, to test the role of IRF6 in NSCL/P susceptibility in an Iranian population, we performed a population based case-control stud.
 
Methods: One-hundred ten patients with NSCL/P and 110 matched healthy subjects were recruited to this population-based study. The IRF6 rs642961 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.
 
Results: Participants did not differ significantly by age and gender
(P > 0.05). The AA, AG, and GG genotypes frequencies of the IRF6 rs642961 polymorphism in the NSCL/P cases were 27.3%, 53.6% and 19.1%, respectively while the corresponding frequencies in the healthy subjects were 34.5, 56.4% and 9.1%, respectively. There was a significant association between homozygote mutant genotype (GG) of IRF6 rs642961 polymorphism and increased risk of NSCL/P (OR = 2.360, 95% CI 1.055-5.280, P = 0.037).
 
Conclusion: the current study suggested that IRF6 rs642961 polymorphism might be associated with susceptibility to NSCL/P in an Iranian population. However, well-designed epidemiological studies with larger sample size are needed to further validate our results.

Keywords


1. 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.
2. 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 Res Part A Clin Mol Teratol 2016; 106(9): 773-88.
3. Mossey PA, Modell B. Epidemiology of oral clefts 2012: an international perspective. Front Oral Biol 2012; 16: 1-18.
4. Yi-shan L, Bin L, Tao L, Kadeer B, Zhong-cheng G, et al. Relationship between genetic polymorphism of MTHFR and cleft lip and palate in Xinjiang population. Chinese J Clin Electron Ed 2013; 7(11): 4795-8.
5. Yuan Q, Blanton SH, Hecht JT. Genetic causes of nonsyndromic cleft lip with or without cleft palate. Adv Otorhinolaryngol 2011; 70: 107-13.
6. Aldhorae KA, Böhmer AC, Ludwig KU, Esmail AH, Al-Hebshi NN, Lippke B, et al. Nonsyndromic cleft lip with or without cleft palate in arab populations: Genetic analysis of 15 risk loci in a novel case-control sample recruited in Yemen. Birth Defects Res Part A Clin Mol Teratol 2014; 100(4): 307-13.
7. Rojas-Martinez A, Reutter H, Chacon-Camacho O, Leon-Cachon RB, Munoz-Jimenez SG, Nowak S, et al. Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population: Evidence for IRF6 and variants at 8q24 and 10q25. Birth Defects Res Part A Clin Mol Teratol 2010; 88(7): 535-7.
8. do Rego Borges A, Sá 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. Am J Med Genet Part A 2015; 167(10): 2344-9.
9. Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet 2011; 12(3): 167-78.
10. Song T, Wu D, Wang Y, Li H, Yin N, Zhao Z. SNPs and interaction analyses of IRF6, MSX1 and PAX9 genes in patients with non-syndromic cleft lip with or without palate. Mol Med Rep 2013; 8(4): 1228-34.
11. Kurosaka H, Iulianella A, Williams T, Trainor PA. Disrupting hedgehog and WNT signaling interactions promotes cleft lip pathogenesis. J Clin Invest 2014; 124(4): 1660-71.
12. Lu Y, Liu Q, Xu W, et al. TGFA and IRF6 Contribute to the Risk of Nonsyndromic Cleft Lip with or without Cleft Palate in Northeast China. Meara JG, ed. PLoS One 2013; 8(8): e70754.
13. Hozyasz KK. The search for risk factors that contribute to the etiology of non-syndromic cleft lip with or without cleft palate (CL/P) in the Polish population. Pediatr Pol 2010; 85(6): 609-23.
14. Richardson S, Khandeparker RV. Management of lip pits in Van der Woude syndrome: a clinical classification with difficulty index. J Oral Maxillofac Surg. 2016;74(9):1849.e1-1849.e10.
15. Ghassibé M, Bayet B, Revencu N, Verellen-Dumoulin C, Gillerot Y, Vanwijck R, et al. Interferon regulatory factor-6: a gene predisposing to isolated cleft lip with or without cleft palate in the Belgian population. Eur J Hum Genet 2005; 13(11): 1239-42.
16. Souto LR. Congenital bilateral lower lip pits associated with fistulae of the minor salivary glands: case report of the principal Van der woude syndrome’s trait. Aesthetic Plast Surg 2008; 32(1): 172-4.
17. Fan R, Flores RL, Faught PR, Lin J. Congenital lower lip pits (van der Woude Syndrome): What pathologists need to know. Pediatr Dev Pathol 2013; 16(5): 343-7.
18. Gurramkonda VB, Murthy J, Syed AH, Lakkakula BV. Lack of association between IRF6 polymorphisms and nonsyndromic oral clefts in South Indian population 2013; 1(1): 2167-77.
19. Wang M, Pan Y, Zhang Z, Wang L. Three polymorphisms in IRF6 and 8q24 are associated with nonsyndromic cleft lip with or without cleft palate: Evidence from 20 studies. Am J Med Genet Part A 2012; 158A(12): 3080-6.
20. 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(Suppl 9): 226S-32S.
21. Brito LA, Bassi CF, Masotti C, Malcher C, Rocha KM, Schlesinger D, et al. IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population. Am J Med Genet Part A 2012; 158A(9): 2170-5.
22. Nouri N, Memarzadeh M, Carinci F, Cura F, Scapoli L, Nouri N, et al. Family-based association analysis between nonsyndromic cleft lip with or without cleft palate and IRF6 polymorphism in an Iranian population. Clin Oral Investig 2015; 19(4): 891-4.
23. Jagomägi T, Nikopensius T, Krjutskov K, Tammekivi V, Viltrop T, Saag M, et al. MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate. Eur J Oral Sci 2010; 118(3): 213-20.
24. Ibarra-Arce A, García-Álvarez M, Cortés-González D, de Zarate-Alarcón GO, Flores-Peña L, Sánchez-Camacho S, et al. IRF6 polymorphisms in Mexican patients with non-syndromic cleft lip. Meta gene 2015;4: 8-16.
25. Birnbaum S, Ludwig KU, Reutter H, Herms S, Steffens M, Rubini M, et al. Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24. Nat Genet 2009; 41(4): 473-7.
26. Rahimov F, Marazita ML, Visel A, Cooper ME, Hitchler MJ, Rubini M, et al. Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. Nat Genet 2008; 40(11): 1341-7.
Volume 1, Issue 1
July 2018
Pages 30-35
  • Receive Date: 24 November 2017
  • Revise Date: 23 June 2017
  • Accept Date: 26 April 2018
  • First Publish Date: 01 July 2018