Numerous studies have explored the independent association of the MTHFR C677T or A1298C polymorphism with various clinical conditions.[1,9–15] The results showed that the 2 polymorphisms can affect diseases risks both positively (such as neural tube defects, coronary heart disease, hypertension, and several cancers)[1,9,10,15] and negatively (such as colorectal, colon, and prostate cancers).[3,39] The relationship between the geographical variations of the C677T polymorphism and the prevalence of related diseases is complicated in China. Here, MTHFR is linked to isolated spina bifida.