Association between MTHFR 677C>T polymorphism and vascular complications in sickle cell disease: A meta-analysis.

Sickle cell disease (SCD) is considered as a vascular disease due to its chronic vascular manifestations such as leg ulcers, priapism, acute chest syndrome (ACS), stroke, retinopathy, renal insufficiency, pulmonary hypertension, avascular necrosis of the femoral head (AVNF) and splenic infarction. Emerging evidence has shown that the MTHFR 677C>T variant allele is associated with vascular complications (VC) in patients with SCD; however, results from individual studies are inconclusive. The aim of this meta-analysis is to evaluate the association between the MTHFR 677C>T polymorphism and the susceptibility for VC in SCD patients. Articles published in English were collected from Medline, PubMed, Embase, and Web of Science databases. As a result, 11 studies in different populations including 614 SCD patients with VC, and 559 patients without VC were selected. Meta-analysis in fixed effect model showed that mutant genotypes (CT+TT vs. CC) of the MTHFR 677C>T polymorphism is associated with increased risk of vascular complication (OR=1.81, 95% CI=1.37-2.40, P<0.001). This study did not demonstrate publication bias or between-study heterogeneity. Our meta-analysis establishes that the MTHFR 677C>T polymorphism as a high-penetrant risk factor for VC in SCD patients. Further research is needed to support the clinical utility of MTHFR genetic testing for predicting VC in patients with sickle cell disease.