The TT genotype of the C677T polymorphism in the methylentetrahydrofolate reductase as a risk factor in thrombotic microangiopathies: results from a pilot study

• Published in: Clinical and applied thrombosis/hemostasis Vol. 15; no. 3; p. 283
• Main Authors: Sucker, Christoph, Kurschat, Christine, Farokhzad, Firuseh, Hetzel, Gerd R, Grabensee, Bernd, Maruhn-Debowski, Beate, Loncar, Robert, Scharf, Rudiger E, Zotz, Rainer B
• Format: Journal Article
• Language: English
• Published: United States 01-06-2009
• Subjects: Adult; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Hemolytic-Uremic Syndrome - enzymology; Hemolytic-Uremic Syndrome - genetics; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Middle Aged; Odds Ratio; Phenotype; Pilot Projects; Polymorphism, Genetic; Purpura, Thrombotic Thrombocytopenic - enzymology; Purpura, Thrombotic Thrombocytopenic - genetics; Risk Assessment; Risk Factors; Severity of Illness Index; Young Adult
• ISSN: 1076-0296
• DOI: 10.1177/1076029607308865

In this study, we assessed the potential role of the TT genotype of the gene of the methylenetetrahydrofolate reductase for the manifestation of thrombotic microangiopathies, enrolling 40 affected patients (mean age [+/- standard deviation] 35 +/- 11 years). As a result, the methylenetetrahydrofolate reductase 677TT genotype was more prevalent in patients with thrombotic microangiopathies compared with controls (adjusted odds ratio = 2.58, 95% confidence interval = 1.2-5.7, P = .018), particularly in those suffering from the hemolytic uremic syndrome. A hemolytic more severe clinical course of thrombotic microangiopathies in carriers of the methylenetetrahydrofolate reductase 677TT genotype was not observed. In summary, our findings suggest a significant influence of the methylenetetrahydrofolate reductase genotype on the manifestation of thrombotic microangiopathies. The 677 TT genotype of this polymorphism appears to be a risk factor for manifestation of these rare thrombotic disorders, possibly explained by endothelial activation and increased oxidative stress.