Homocysteine Metabolism Abnormality With Pathogenesis Of Coronary Heart Disease

Object To study the relationship among plasma homocystein(HCY), folate, vitamine B₁2, C677T mutation of the methylenetetrahydrofolate reductase(MTHFR) gene, the T833C,G919A mutation of the cystathionine-β-synthase(CBS) gene and coronary heart disease.Methods Plasma homocystein(HCY) were determined by enzyme linked irnmunosorbent assay(ELISA), plasma folate and vitamine B₁2 as cofactors of MTHFR and CBS were determined by radioimmunologic assay, genomic DNA abstract with methods of guanidine hydrochloric acid .The mutation of the 677C-T transition of MTHFR was investigated by using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP), the mutation of the 833T-C, 919G-A transition was identify with amplification refractory mutation system(ARMS) methods.Results The plasma HCY mean levels of 107 patients in CHD group were 21.58?2.69umol/L, in control group are 14.86 + 8.37umol/L. They are higher in CHD group than those in control group(p<0.01). The mean level of folate and vitamineBn are lower in CHD group(2.78?1.66ng/ml, 231.76?143.78pg/ml) than those in control group(8.78?.69 ng/ml, 508.71 ?47.37 pg/ml)(p<0.01). Thegenotype frequencies of MTHFR were 28.1% for TT, 38.3% for TC and 33.6% for CC in CHD group, respectively, while 20.8% for TT, 41.7% for TC and 37.5% for CC in control group. There was no significant difference in the frequencies of genotype and alleles between two groups( x 2=1.427, p>0.05; x 2=1.257, p>0.05). 9 C homogenotype of CBS gene T833C was found ,26 heterogenetic type was found and 72 T homogenotype was found in CHD group, and 2,9,85 in control group, respectively. There were obvious differences in frequencies of genotypes and alleles of the two groups ( x 2=13.271, p<0.005; x 2=15.916, p<0.005). 6 A homogenotype of CBS gene G919A was found , 22 heterogenetic type was found and 79 G homogenotype was found in CHD group, and 2,9,85 in the control one, respectively. There were significant differences in frequencies of genotypes of the two groups ( x 2=7.098, p<0.05; x 2= 8.218, p<0.005). There were obvious differences in HCY levels among the three genotype of MTHFR gene in CHD group(F=4.269,p=0.026), but there was no difference in control group (F=1.235,p=0.623). The plasma HCY levels in TT genotype of MTHFR gene were much higher than those in CC(q=3.892,p=0.013), but no difference between the levels in TC and CC. There were obvious differences in HCY levels among the three genotype of CBS T833C gene in CHD group(F=3.984,p=0.037), there was no difference in control group (F=1.173,p=0.563). The plasma HCY levels hi CHD group of CC genotype were much higher than those in TT(q=3.714,p=0.047). The plasma HCY levels in CHD group of CT genotype were much higher than those in TT(q=3.896,p=0.023). There were obvious differences in HCY levels among thethree genotype of CBS G919A gene in CHD group(F=3.402,p=0.041), there was no difference in control group (F=1.032,p=0.423).Plasma HCY concentrations are higher markedly in patients with homozygosity(AA) and heterozygosity(AG) of the G919A mutation than those in patients without mutations(GG) (q=4.014,p=0.025; q=3.895,p=0.012).Conclusions (l)Hyperhomocysteinemia is an independent risk factor of CHD. Hyperhomocysteinemia is related with folate and vitamineBu decreasing. (2)MTHFR and CBS are the main enzymes related to homocysteine metabolism. Their genetic mutations are possibly important mechanism of hyperhomocysteinemia.(3) MTHFR mutation is not related with coronary heart disease, CBS mutation is related with it.