Genetic Predictors for the Development of Congenital Orofacial Clefts

Nadezhda I. Pavlova, Khariton A. Kurtanov, Aleksandra T. Diakonova, Lyubov S. Mironova, Natalia A. Solovyeva, Yigulana P. Borisova, Vladimir V. Dodokhov, Innokenty D. Ushnitsky

International Journal of Biomedicine. 2020;10(1):50-53.
DOI: 10.21103/Article10(1)_OA7
Originally published March 15, 2020


Background: The aim of this study was to search for associations between polymorphisms of the IRF6, MDR1, and MTHFR genes and the risk of congenital orofacial cleft (OFCs) among the population of the Republic of Sakha (Yakutia).
Methods and Results: The sample of the studied individuals consisted of 94 children (46 girls and 48 boys) with OFCs and their parents (75 mothers and 18 fathers). The children with OFCs were divided into 3 groups. Group 1 included 48 children with cleft lip and palate (CLP); Group 2 included 22 children with cleft lip (CL); Group 3 included 24 children with cleft palate (CP). The comparison group included 156 healthy volunteers (118 women and 38 men) who did not have a history of relatives with OFCs.
Analysis of the distribution of alleles and genotypes of studied SNPs in children with all OFCs and healthy children showed a significant (P=0.000) difference only in MDR1 genetic variant rs1045642 SNP. The carriage of the TT genotype of the MDR1 rs1045642 SNP was associated with increased risk of OFCs (OR=2.711, 95% CI=1.459-5.037; P=0.000). Analysis of the frequency distribution of alleles and genotypes depending on the severity of clefts showed that the carriage of the TT genotype of the MDR1 rs1045642 SNP was associated with significant risk for development of CL (OR = 3.114; 95% CI = 1.123-8.634) and CLP (OR = 2.804; 95% CI = 1.333-5.895). In children with CP, we found significant risk with carriage of the TT genotype of the IRF6 rs2235371 SNP (OR = 5,429, 95% CI = 1,135-25,962; P=0.035).
Conclusion: A study of four SNPs in the IRF6, MDR1, and MTHFR genes revealed statistically significant increased risks for OFCs in carriers of the TT genotype of the MDR1 rs1045642 SNP; in addition, the carriage of the TT genotype of the IRF6 rs2235371 SNP significantly increased the risk of CP development.

orofacial cleft • cleft lip and palate • IRF6 • MTHFR • MDR1
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Received January 9, 2020.
Accepted February 16, 2020.
©2020 International Medical Research and Development Corporation.