Relationship between MTHFR C677T, homocysteine, and ischemic stroke in a large sample of the Han Chinese population

Abstract

Ischemic stroke, one of the prevalent causes of death and disability worldwide, is linked to environmental and genetic factors, including polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism. The present study aimed to explore the relationship between the MTHFR C677T variant, plasma homocysteine, and risk of developing large-artery atherosclerotic ischemic stroke (LAAIS) among Han Chinese.A population-based case-control study, which included 1810 patients with LAAIS and 1765 unrelated control subjects, was conducted. Compared to the controls, LAAIS patients had a significantly higher prevalence of hypertension, diabetes mellitus, smoking, and alcohol consumption (P < .001), as well as significantly higher mean fasting blood glucose, triglyceride, total cholesterol, and plasma homocysteine levels (P < .001). The TT homozygous genotype correlated with increased risk of developing LAAIS, as indicated by a significantly higher odds ratio (OR) compared to the CT and CC genotypes, in both additive (OR = 3.215, P = .01) and recessive models (OR = 3.265, P = .01). The plasma homocysteine level was genotype-dependent according to the following trend: TT > CT > CC.In conclusion, our data demonstrate that, in spite of its low prevalence in both patients and controls (1.5% vs 0.8%), the MTHFR C677T variant could, at least in part, affect homocysteine levels and this, either alone or in combination with other factors, increases the risk of LAAIS.

Cerebellar stroke in a young female associated with elevated homocysteine levels and heterozygous MTHFR <em style="mso-bidi-font-style: normal;">C677T</em> gene:&nbsp; A case report.

“…In a Chinese study among a large population of ischemic stroke patients, a significant association with elevated homocysteine has been demonstrated, and the level of homocysteine was observed to be highest with TT variant which was followed by CT and CC variants. Although both TT and CT variants were correlated with stroke, only the TT variant had a significant association with an increased risk of ischemic stroke [3]. Therefore, in the absence of other possible causes of ischemic stroke in this young patient the presence of MTHFR C677T gene mutation and hyperhomocysteinemia despite the normal vitamin B12 level is the most likely cause for the ischemic cerebellar stroke.…”

“…Defects in this enzyme, folate deficiency or vitamin B12 deficiency can result in elevated homocysteine levels [2]. Elevated homocysteine levels as a cause of thrombosis are recognized [5,3]. The mechanism of it is yet to be understood.…”

“…MTHFR gene mutation could be homozygous(T677T) or heterozygous(C677T). The homozygous mutation is associated with higher homocysteine levels than the heterozygous mutation, hence correlating with a higher risk of thrombosis [3]. A deficiency of folate or vitamin B12 can augment the enzyme deficiency in a heterozygous mutation.…”

“…Homocysteine is an amino acid produced in methionine metabolism, of which the rate-limiting enzyme is methylenetetrahydrofolate reductase, encoded by the MTHFR gene [2]. Mutations of this gene can cause elevated levels of homocysteine, especially the homozygous MTHFR T677T variant [3]. We report a case of a young female having heterozygous MTHFR C677T gene mutation and elevated level of homocysteine presented late with a right cerebellar ischemic stroke.…”

Polimorfismo de proteína 5,10-metilentetrahidrofolato reductasa en población venezolana

“…Aunque se desconocen los mecanismos exactos, su deficiencia genera implicaciones graves que afectan tanto a la madre como al recién nacido al alterar procesos claves en esta etapa como es la síntesis y reparación del DNA así como la estabilidad y funcionalidad (expresión génica y mutaciones) del mismo, afectando también la síntesis de proteínas y otros compuestos e incrementando el estrés oxidativo (6) . La disminución del folato y el aumento de los niveles plasmáticos de Hcy están asociados con una variedad de afecciones comunes, tales como enfermedades cardiovasculares (7) , defectos del tubo neural (6,8) , labio o paladar hendido (9) , hipertensión (10) , preeclampsia y complicaciones del embarazo (11,12) , trombosis (13) , trisomìa 21 (14) , depresión /esquizofrenia (15,16) , autismo (17) , neuropatía diabética (18) , ACV isquémico (19) y enfermedades gastrointestinales (20) , entre otras.…”