Background: MTHFD1L gene encoded a mitochondrial enzyme that plays a crucial role in the production of tetrahydrofolate within the mitochondria. However, research on the association between MTHFD1L gene variations and hypertension risk is limited.
Methods: This study included a total of 723 participants, consisting of 367 healthy individuals and 356 individuals diagnosed with hypertension. Four single nucleotide polymorphisms (SNPs) within MTHFD1L (rs803419, rs6922269, rs1555179 and rs11155772) were selected and genotyped by Agena MassARRAY platform. Logistic regression analysis was employed to determine the odds ratios (OR) and 95% confidence intervals (CI), assessing the potential association between these MTHFD1L SNPs and the predisposition to hypertension. Furthermore, the multifactor dimensionality reduction (MDR) method was utilized to analyze the combined effects of MTHFD1L SNP interactions on hypertension risk.
Results: MTHFD1L rs6922269 (p = 9.37 × 10-6, OR = 3.15) and rs1555179 (p = 7.14 × 10-7, OR = 0.59) were associated with hypertension risk. Interestingly, rs6922269 was more significantly related to an increased hypertension risk in females, whereas rs1555179 was more significantly associated with a reduced risk in males. Moreover, rs803419 might contribute to a reduced susceptibility to hypertension in females. Notably, rs1555179 was the most informative single-locus model for hypertension risk with an information gain (IG) of 2.44%.
Conclusion: Our findings indicated that MTHFD1L rs6922269 and rs1555179 were associated with hypertension risk among the Chinese Han population. These results contribute to a deeper understanding about the role of MTHFD1L gene in hypertension occurrence.
Keywords: Hypertension; MTHFD1L; SNP-SNP; genetic variants; susceptibility.