Association between MTHFR gene polymorphisms and H-type hypertension in patients with ischemic stroke

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in homocysteine metabolism. Its 677C>T and 1298A>C polymorphisms can reduce enzyme activity, potentially elevating homocysteine levels. H-type hypertension (hypertension with homocysteine ≥10 μmol/L) is an important risk factor for ischemic stroke, and its synergistic effect exacerbates vascular damage. However, the association between these MTHFR polymorphisms and elevated homocysteine levels in patients with hypertension complicated by ischemic stroke remains unclear. This study aimed to investigate the association between MTHFR gene polymorphisms and H-type hypertension in patients with ischemic stroke.

A total of 215 patients with ischemic stroke and hypertension admitted to the Department of Neurology at the Taian City Central Hospital from June 2021 to December 2022 were enrolled. General clinical data and biochemical indicators were collected. MTHFR genotyping was performed using a universal sequencing kit and a TL998A fluorescence detector. Linkage disequilibrium was analyzed via SHEsis software. Statistical analyses were conducted using SPSS 25.0. P < 0.05 indicates that the difference is statistically significant.

Among patients with ischemic stroke combined with hypertension in this region, the proportion of H-type hypertension was 89.3%. The proportion of males in the H-type hypertension group was significantly higher than in the non-H-type hypertension group (P < 0.05). The genotype and allele distributions of MTHFR (677C>T) (risk allele: T) differed significantly between groups (P < 0.05): the H-type group had a higher frequency of the TT genotype (47.4% vs. 17.4%) and T allele (67.2% vs. 50.0%). Multivariate logistic regression analysis showed that the MTHFR (677C>T) TT genotype was an independent risk factor for H-type hypertension (P = 0.021, OR = 2.615, 95%CI [1.154-5.926]). For haplotypes with a frequency >3%, there were three haplotypes of MTHFR (677C>T)/(1298A>C). The C-A haplotype was a protective factor for H-type hypertension (P = 0. 028, OR = 0.485, 95%CI [0.252-0.934]), while the T-A haplotype was a risk factor (P = 0.022, OR = 2.029, 95%CI [1.096-3.756]).

In patients with ischemic stroke, the MTHFR (677C>T) TT genotype is an independent risk factor for H-type hypertension. For haplotypes with a frequency >3%, the C-A haplotype was a protective factor for H-type hypertension, whereas the T-A haplotype was a risk factor.