Polymorphisms Of Enzymes Related To Homocysteine Metabolism In Patients With Coronary Heart Disease

Objective To study the relationship among polymorphism of 28bp tandem repeat sequence in 5'-UTR and 6-bp variation at bp1494 in the 3'-UTR of thymidylate synthase(TS), a mutation at nucleotide 677 in methylenetetrahydrofolate reductase(MTHFR) , plasma homocysteine (Hcy) levels and coronary heart disease.MethodsAll the subjects were underwent coronary angiography. Subjects (n=122) with≥50% stenosis in at least one coronary vessels were defined as CHD . Subjects (n=56) without any stenosis in all coronary vessels were defined as controls. TS 5'-UTR 28bp tandem repeat sequence gene polymorphism was analyzed using PCR and TS3'-UTR 6bp variation and MTHFR genotyping was performed using PCR and restriction fragment length polymorphism analysis(RFLP). Total plasma Hcy levels were measured by HPLC (high –performance liquid chromatography, HPLC) with fluorescence detection. ResultsMean total plasma homocysteine concentration was significantly higher in CHD patients (12.99±4.76μmol/L)than that in controls(10.95±4.75μmol/L) (P=0.009<0.05).There was significant difference in TS5'-UTR 28bp tandem repeat sequence genotype frequencies between CHD group and controls respectively(P=0.029<0.05). In the CHD group, the Hcy levels of different TS28 genetypes is higher than that in controls (P=0.03<0.05). In the CHD group, the Hcy levels of 3R/3R is higher than that of 2R/2R(P<0.001) and Hcy levels of 3R/2R is higher than that of 2R/2R(P=0.011<0.05). There is no difference of the Hcy levels between 3R/3R and 3R/2R(P=0.979>0.05).No significant difference in TS3'-UTR 6bp variation genotype frequencies between the two groups was observed (P=0.285>0.05). In the CHD group, the Hcy levels of different TS6 genetypes is higher than that in controls (P=0.006<0.05). In CHD group, there was no significant difference between the Hcy levels in the individuals with the genetypes of +6bp/+6bp, +6bp/-6bp, -6bp/-6bp.There were three kinds of genetypes of MTHFR :TT TC CC. The frequencies of the three genetypes were significantly different between CHD groups and controls (P=0.046<0.05).The frequency of T allele was significantly higher in CHD than that in controls(P=0.039<0.05). In the two groups, the difference of the Hcy levels among the three genetypes is significant (P<0.001). In the CHD group, the Hcy levels with TT were significantly higher than that in individuals with TC (P=0.003<0.05) and CC (P=0.001<0.05). However, there was no significantly different of Hcy levels between individuals with TT and individuals with CC (P=0.99>0.05).Conclusion Hyperhomocysteinemia is associated with CHD. Polymorphism of 28bp tandem repeat sequence in the TS 5'-UTR correlates with CHD and it may be a possibly genetics factor of CHD. The mutation in the nucleotide 677 in MTHFR correlates with CHD . It may be a possibly genetic factor of CHD. Allele T is associated with the Hcy level in CHD group.