01 February 2016 : Clinical Research
Effect of MTHFR Gene Polymorphism Impact on Atherosclerosis via Genome-Wide Methylation
Xuefeng LinBC, Wei ZhangCE, Qun LuDE, Xinjun LeiEF, Tingzhong WangFG, Xuanmao HanAF, Aiqun MaABCDDOI: 10.12659/MSM.895296
Med Sci Monit 2016; 22:341-345
Abstract
BACKGROUND: Atherosclerosis 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 AND METHODS: Blood 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.
RESULTS: LINE-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).
CONCLUSIONS: MTHFR C667T loci polymorphism may affect atherosclerosis by regulating genome methylation level.
Keywords: Electrophoresis, Agar Gel, DNA Methylation - genetics, Atherosclerosis - genetics, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Linkage Disequilibrium - genetics, Long Interspersed Nucleotide Elements - genetics, Methylenetetrahydrofolate Reductase (NADPH2) - genetics, Polymorphism, Single Nucleotide - genetics
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