Professor Huang Hui's Team Reveals the Impact of Plateletcrit and Methylenetetrahydrofolate Reductase C677T Genotype on the Efficacy of Folic Acid in Preventing First Stroke
Recently, Professor Huang Hui's team published a research paper titled "Effect of plateletcrit and methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on folic acid efficacy in stroke prevention" in Signal Transduction and Targeted Therapy (an Academia Sinica A journal, Impact Factor = 39). This study aimed to investigate whether platelet activation parameters and MTHFR genotypes jointly influence the efficacy of folic acid treatment in preventing first-time strokes.
Approximately 50% of deaths related to cardiovascular and cerebrovascular diseases are strongly linked to hypertension, making it one of the leading causes of death. Stroke is the most common cardiovascular event in hypertensive patients. Hyperhomocysteinemia is recognized as an important risk factor for stroke. Current clinical guidelines suggest that folic acid can reduce serum total homocysteine (tHcy) levels, thereby lowering the risk of stroke. However, not all hypertensive patients with elevated tHcy benefit from folic acid supplementation. MTHFR is a key factor in folate metabolism. The MTHFR gene contains a single nucleotide polymorphism, C677T, which causes reduced enzyme activity and heat tolerance, leading to elevated tHcy levels. Due to impaired folate utilization, individuals carrying the MTHFR C677T mutation are less responsive to folic acid treatment. The prevalence of the MTHFR 677 TT genotype in hypertensive adults in China is significantly higher than in other countries. Folate supplementation that lowers tHcy levels and platelet activation, while considering MTHFR C677T genotype polymorphisms, is a critical strategy for stroke prevention and is the most cost-effective and efficient method to reduce the high incidence of stroke in China.
However, the comprehensive effects and clinical significance of platelet activation parameters and MTHFR C677T genotype on folic acid treatment for stroke prevention have not been systematically studied. Therefore, this study aimed to identify the subgroup of hypertensive patients who would most benefit from folic acid treatment to reduce the risk of first-time stroke by considering both MTHFR C677T genotype and platelet activation parameters.
The study included 11,185 adult hypertensive patients with relevant platelet activation parameters and MTHFR genotype data. When considering platelet activation parameters (plateletcrit, platelet count, mean platelet volume, and platelet distribution width) and MTHFR genotype, the subgroup with low plateletcrit (Q1) and TT genotype had the highest stroke incidence (5.6%). This subgroup showed significant benefit from folic acid treatment, with a 66% reduction in first stroke risk (HR: 0.34; 95% CI: 0.14-0.82; p = 0.016). Consistent with this, the subgroup with low plateletcrit (Q1) and CC/CT genotype also benefited from folic acid treatment (HR: 0.40; 95% CI: 0.23-0.70; p = 0.001). Therefore, the study suggests that in hypertensive adults in China, low plateletcrit is an effective marker to identify patients who may benefit most from folic acid treatment, especially those with the TT genotype, the subgroup at the highest risk for stroke.
PhD students Shi Yuncao and Zhang Zhengzhipeng are the co-first authors of the paper, with Professor Huang Hui as the corresponding author. The Eighth Affiliated Hospital of Sun Yat-sen University is the first author and corresponding author institution.
The research was supported by the National Natural Science Foundation of China (grant numbers: 82330021, 82061160372, 82270771) and several other grants.
