Association between MTHFR polymorphisms and orofacial clefts risk: a meta-analysis

Area of Science:

• Genetics
• Public Health
• Reproductive Medicine

Background:

• The methylenetetrahydrofolate reductase (MTHFR) gene plays a crucial role in folate metabolism.
• Polymorphisms C677T and A1298C in the MTHFR gene are investigated for their association with orofacial clefts (OFCs).
• Previous studies on MTHFR gene variants and OFCs risk have yielded conflicting results.

Purpose of the Study:

• To conduct a comprehensive meta-analysis to clarify the association between MTHFR gene polymorphisms (C677T and A1298C) and the risk of OFCs.
• To resolve inconsistencies in existing research regarding the genetic contribution to OFCs.
• To investigate potential ethnic and demographic differences in this association.

Main Methods:

• A systematic literature search was conducted across PubMed, EmBase, and Medline databases up to October 31, 2011.
• Meta-analysis using fixed-effects or random-effects models was employed to calculate pooled odds ratios (ORs).
• Genetic comparisons included heterozygous vs. wild type and homozygous vs. wild type for MTHFR polymorphisms.

Main Results:

• A total of 18 studies were included in the meta-analysis.
• No significant association was found between infant and maternal MTHFR C677T and A1298C variants and the risk of cleft lip with or without palate (CL/P) or cleft palate only (CPO).
• An exception was the maternal 677TT genotype for CL/P (OR=1.32), which showed a statistically significant association. This association remained significant in subgroup analyses of the white population (OR=1.36).

Conclusions:

• Maternal MTHFR 677TT genotype may be associated with an increased risk of CL/P in offspring within the white population.
• The study suggests a potential role for specific MTHFR genotypes in OFCs etiology, particularly in certain ethnic groups.
• Further research is warranted to confirm these findings and elucidate the underlying mechanisms.