Association of a Polymorphism in the Gene Encoding Methylenetetrahydrofolate Dehydrogenase 1 (MTHFD1) 1958G>A with Orofacial Cleft

Abstract

Objective: To evaluate the possible association of a polymorphism in the gene encoding methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), 1958G>A, with the susceptibility to orofacial cleft in an Indonesian population. Material and Methods: A total of 200 stored secondary biological samples from 30 cases of orofacial cleft and 170 unaffected controls were analyzed to determine the polymorphism status at base 1958. The analysis was conducted using the PCR-restriction fragment length polymorphism technique after digestion with the Msp1 restriction enzyme. The samples were then subjected to agarose gel electrophoresis to investigate the presence or absence of the following fragments: genotype GG, 196, 86 and 40 base pairs (bp); genotype AA, 282 and 28 bp and genotype AG, 282, 196, 86, 40 and 28 bp. The test groups were compared using the Chi-square test. Results: The wild-type allele containing 1958G, as well as the genotype GG, were significantly more common in the control group than in the orofacial cleft group. Conclusion:The MTHFD1 1958G>A polymorphism was significantly associated with orofacial cleft susceptibility in the tested Indonesian population.

Association Between MTHFD1 1958G > A Variant and non-Syndromic Cleft lip and Palate: An Updated Meta-Analysis

“…On the basis of the initial searches, a total of 104 publications were retrieved from the source databases (Figure 1). After a detailed evaluation, 10 papers analyzing the associations between MTHFD1 1958G > A variant and NSCLP risk were included in the meta-analysis (Mills et al, 2008; Palmieri et al, 2008; Bufalino et al, 2010; Mostowska et al, 2010; Zhao et al, 2013; de Aquino et al, 2014; Murthy et al, 2014b; Nan et al, 2014; Wu et al, 2015; Auerkari et al, 2021). To determine the source of heterogeneity, a subgroup analysis based on ethnicity was performed.…”

“…However, the studies are not consistent in reporting the link between the MTHFD1 1958G > A variant and NSCLP. Some studies found a link between the 1958G > A variant and NSCLP (Mostowska et al, 2006; Boyles et al, 2008; Murthy et al, 2014b; Wu et al, 2015; Auerkari et al, 2021), while others found no link (Mostowska et al, 2006; Boyles et al, 2008; Palmieri et al, 2008; Mostowska et al, 2010; Zhao et al, 2013; de Aquino et al, 2014; Nan et al, 2014;).…”