Effect of MTHFR Gene Polymorphism Impact on Atherosclerosis via Genome-Wide Methylation

Abstract

BackgroundAtherosclerosis seriously threats human health. Homocysteine is an independent risk factor closely related to DNA methylation. MTHFR C667T loci polymorphism is closely associated with homocysteine level. This study aimed to investigate the relationship among MTHFR C667T loci polymorphism, genome-wide methylation, and atherosclerosis.Material/MethodsBlood sample was collected from 105 patients with coronary atherosclerosis and 105 healthy controls. Pyrosequencing methylation was used to detect LINE-1 methylation level. Polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP) was used to test MTHFR.ResultsLINE-1 methylation level in the patient group was significantly lower than in the controls (t=5.007, P<0.001). MTHFR C667T genotype distribution presented marked differences in the 2 groups. TT genotype carriers had significantly increased risk of atherosclerosis (OR=3.56, P=0.009). Three different genotypes of MTHFR C667T loci showed different LINE-1 methylation level between the 2 groups (P<0.01). LINE-1 methylation level in TT and CT genotype carriers was obviously lower than in CC genotype carriers (P<0.05).ConclusionsMTHFR C667T loci polymorphism may affect atherosclerosis by regulating genome methylation level.

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“…It is important to note however that the studies included in this meta-analysis were designed to examine a number of diseases and were not focused on hypertension alone [67]. Elsewhere, long interspersed element-1 (LINE-1) methylation (an indication of global methylation) has been reported to be significantly lower in individuals with the MTHFR 677TT genotype compared to those with the CC genotype [68]. Furthermore, adults with the TT genotype compared to the CC genotype had diminished genomic DNA methylation, and this correlated with folate status [66].…”