5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational genetic association studies
PubMed 10791559 · doi:10.1093/oxfordjournals.aje.a010290
What was done
The authors conducted a Human Genome Epidemiology (HuGE) review and meta-analysis examining the population prevalence of MTHFR gene variants (C677T and A1298C) and their associations with congenital anomalies, including spina bifida, oral clefts, Down syndrome, and fetal anticonvulsant syndrome.
What was found
MTHFR C677T homozygosity frequency ranged from ≤1% in Black populations from Africa and the US to ≥20% in Italians and US Hispanics. Infant C677T homozygosity was associated with spina bifida (pooled OR = 1.8; 95% CI: 1.4, 2.2). Maternal C677T homozygosity was also associated with spina bifida (pooled OR = 2.0; 95% CI: 1.5, 2.8). Evidence for oral clefts, Down syndrome, and fetal anticonvulsant syndrome was conflicting or unreplicated.
Why it matters
It demonstrates that both infant and maternal MTHFR C677T homozygosity are moderate genetic risk factors for spina bifida, linking folate metabolism genetics to neural tube defect risk.
Limits
The abstract does not state the total number of studies or sample size. The effect may be modified by maternal nutritional folate status or interactions with other folate pathway genes, which were not fully delineated.
Cited by
- context Between 25% and 28% of people carry an MTHFR polymorphism.