Allelic and Genotypic Distribution of rs1801133 in the Methylene Tetrahydrofolate Reductase (MTHFR) Gene Among Family Trios Affected by Nonsyndromic Cleft Lip and Palate

非综合征性唇腭裂家族三联体中亚甲基四氢叶酸还原酶 (MTHFR) 基因 rs1801133 的等位基因和基因型分布

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Abstract

Cleft lips and/or palates are common congenital anomalies with different prevalence across different populations and geographic regions. The present study analyzed the allelic and genotypic frequencies of the MTHFR rs1801133 polymorphism in familial cleft lip and/or palate trios. This retrospective genetic family-based study was carried out in a population-specific background using samples collected from the data bank of 4,000 patient records from a high-volume craniofacial hospital. Forty familial case-parent trios (n = 120 subjects, 40 unaffected fathers, 40 unaffected mothers, and 40 affected children) were selected. Genomic DNA was extracted from peripheral blood samples, and genotyping of the MTHFR rs1801133 polymorphism was carried out using the polymerase chain reaction-restriction fragment length polymorphism method. Allelic and genotypic frequencies were calculated using IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 26. Armonk, NY: IBM Corp., with descriptive statistical analyses applied. Hardy-Weinberg equilibrium and the transmission disequilibrium test were performed using PLINK 1.9 (Purcell Lab, Harvard Medical School). The CC genotype was found to be the most common in all three groups (72.5% of fathers, 85.0% of mothers, and 90.0% of affected children), according to the genotype distribution of the MTHFR rs1801133 polymorphism among the 40 case-parent trios. The CT genotype was observed in 27.5% of fathers, 15.0% of mothers, and 10.0% of affected children. The C allele was observed more commonly in mothers (92.5%), fathers (86.25%), and affected children (95.0%). The T allele was observed in 13.75% of fathers, 7.5% of mothers, and 5.0% of affected children. Transmission disequilibrium test analysis showed no statistically significant preferential transmission of the T allele (OR = 0.4, p = 0.1088), indicating no association. This study contributes to global data on ethnic variation, helping researchers compare populations and design more accurate, population-specific genetic studies.

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