MTHFR and MDR1 Gene Polymorphisms in Yakut Patients with Non-Syndromic Orofacial Clefts

Aleksandra T. Diakonova, Nadezhda I. Pavlova, Vladislav A. Alekseev, Lyubov S. Mironova, Khariton A. Kurtanov, Vladimir V. Dodokhov, Innokenty D. Ushnitsky

International Journal of Biomedicine. 2021;11(4):576-580.
DOI: 10.21103/Article11(4)_OA29
Originally published December 10, 2021


The aim of our study was to investigate the relationship between the MDR1 and MTHFR gene polymorphisms and non-syndromic cleft lip with or without cleft palate (NSCL/P) in the Yakut population in the Republic of Sakha (Yakutia).
Methods and Results: The sample of examined persons consisted of 60 children with NSCL/P. The NSCL/P group was divided into the CLP (cleft lip with cleft palate) subgroup (n=31), CLO (cleft lip only) subgroup (n=14), and CPO (cleft palate only) subgroup (n=15). The comparison group (control) included 174 healthy volunteers who did not have relatives with OFCs. The study of the MDR1 rs1045642 SNP and the MTHFR rs1801133 SNP was performed by PCR and RFLP analysis.
Analysis of the frequency distribution of alleles and genotypes depending on the severity of clefts showed that the carriage of the TT homozygous genotype of the MDR1 rs1045642 SNP was associated with significant risk for the development of NSCL/P (OR=2.52, 95% CI: 1.19-5.32, P=0.02). Analysis of the recessive model (TT vs CC + TC) also found a significant risk of NSCL/P with the TT genotype carriage (OR=2.20, 95% CI: 1.06-4.57, P=0.04). Analysis of the over-dominant model (TC vs TT + CC) showed that the heterozygous TC genotype had a protective effect (OR=0.41; 95% CI: 0.22-0.77, P=0.01) on the development of NSCL/P.
Subgroup analysis according to NSCL/P subtypes (CLO, CPO and CLP) showed that the MDR1 rs1045642 SNP was significantly associated with a high risk of CPO in three genetic models: heterozygous [(TT vs TC): OR=5.03; 95% CI: 1.55-16.32; P=0.01], recessive [(TT vs CC + TC): OR=3.96; 95% CI: 1.32-11.95; P=0.02], and over-dominant [(TC vs TT + CC): OR=0.23; 95% CI: 0.08-0.66; P=0.01].
Conclusion: A study of two SNPs in the MDR1and MTHFR genes revealed a statistically significant increased risk for NSCL/P in carriers of the TT genotype of the MDR1 rs1045642 SNP.

orofacial cleft • MDR1 gene • MTHFR gene • single nucleotide polymorphism
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Received October 31, 2021.
Accepted November 15, 2021.
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