Objective To assess whether the promoter region of the serotonin transporter gene (5-HTTLPR), G-protein beta3 subunit (GNβ3 C825T), 5, 10-methylenetetrahydro folate reductase(MTHFR C677T) andα-adducin gene Gly460Trp (ADDUCI G460W) polymorphisms are associated with the covariation between depressive episode and coronary heart disease and explore the genetic mechanism conceming the pathogenesis of this disorder, as well as to assess the relation between these polymorphisms and the syndrome of blood stasis/ phlegm stagnation type of this disorders.Methods 1. Patients suffering from depression (n=180), Patients suffering fro coronary heart disease(n=171), Patients suffering from coronary heart disease with depressive episode (n=153) and controls (n=156) were grouped and compared in this study. Then, according to differentiation of symptoms and signs of traditional Chinese medicine, we selected paitients with the syndrome of blood stasis(n=ll5) and phlegm stagnation type(n=120).2. The genotypes were determined with polymerase chain reaction(PCR) and allele-specific restriction enzyme analysis. Genotype and allele frequency comparisons between patient groups and control subjects were carried out with chi-square test, as well as using Logistic regression analysis to correct the effect of other risk factor on coronary heart disease and depressive episode.Results 1. The 5--HTTLPR S-allele in patients with depressive episode was significantly more frequent as compared with control subjects (P<0.05)2. Analysis of GNβ3 C825T allelic distribution revealed that the T-alleles in all patient groups were significantly more frequent as compared with healthy controls (P<0.05).3. The frequencies of ADDUCI 460W allele in Patients suffering from coronary heart disease and coronary heart disease with depressive episode were significantly higher than those in the controls (P<0.05).4. Compared the data of same disease with different syndrome showed that the frequencies of GNβ3 825T allele in the syndrome of phlegm stagnation group were significantly more frequent than those in healthy controls (x~2=4.568, P=0.033), and the frequencies of ADDUCI 460WW genotype and W-allele in the syndrome of blood stasis group were significantly more frequent as compared with healthy controls(P<0.01).5. Compared the polymorphisms of different diseases with the same syndrome to those of healthy controls, the results showed that the frequencies of GNβ3 825T allele in the syndrome of phlegm stagnation group suffering from coronary heart disease with depressive episode were significantly higher than those in the controls [(x~2=1.884, P=0.170); (x~2=4.124, P=0.042)], as well as ADDUCI 460W allele in the syndrome of blood stasis with coronary heart disease or coronary heart disease with depressive episode were significantly more frequent than those in the controls[(x~2=6.414, P=0.011); (x~2=10.250, P=0.001)].6. Nosignificant difference for the genotype distribution or the frequency of MTHFR C677T were revealed when comparing controls with all patient groups.Conclusions 1. Our findings suggest that the 5-HTTLPR polymorphism was only related with depressive episode2. ADDUCI G460W was possibly the predisposing gene of coronary heart disease.3. GNβ3 C825T may mediate the covariation between depressive episode and coronary heart disease.4. The etiology of the syndrome of phlegm stagnation of coronary heart disease with depressive episode may be associated with GNβ3 C825T polymorphism.5. This finding support the presence of ADDUCI 460WW genotype may increase the risk of the syndrome of blood stasis in patients suffering from coronary heart disease or coronary heart disease with depressive episode.
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