| Homocystcine (Hcy) is a kind of sulfur-containing amino acids,which is an important intermediate product in the metabolism of methionine and cysteinc.A large number of studies pay close attention to the factors affectting Hcy levels.In general.they can be divided into genetic and non-genetic factors. Previously,more and more researches have shown that hyperhomocysteinemia (HHcy) is an independent risk factor of cardiovascular and cerebrovascular diseases.Objective:Our aims were,1) to investigate the effect of benazepril on plasma homocysteine (Hcy) levels and to analyze the correlation between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and changes in Hey levels in response to benazepril in the rural area of Anhui province.2) to investigate the major risk factors of stroke in Anhui province.and further identified the association between Hcy-related-genes and stroke risks in Chinese.Our findings will provide a strategy for effective prevention and treatment of stroke in the region.Method:A total of 231 patients with mild to moderate essential hypertension were enrolled from Huoqiu and Yuexi, and benazepril was orally administered at a dose of 10 mg/d for 2 weeks. Plasma Hcy levels were measured by high-performance liquid chromatography at baseline and after 2 weeks of treatment. Genotyping of the MTHFR C677T polymorphism was performed by TaqMan probe technique.And a case-control study was designed to investigate 544 subjects,of them,252 ischemic stroke (IS),91 hemorrhagic stroke(HS), and 201 healthy controls.All the subjects were surveyed with questionnaires and taken physical examinations.laboratory parameters including blood-testing results in thefirst 24 hours at admission.Hcy-related-genes(MTHFR C677T, MTHFR A1298C, MTR A2756G. MTRR A66G) polymorphism were genotyped by PCR-RFLP. Both ULR and generalized multifactor dimensionality reduction (GMDR) were used to test the gene-gene interactions on stroke risk.Results:There was no significant change in Hcy level after benazepril treatment for 2 weeks (P<0.97). However, stratifiedby baseline Hcy levels, the patients with baseline Hcy<10 mmol/L had a significant increase in plasma Hcy levels (P<0.003). The results from the multivariable linear regression analysis demonstrated a significant correlation between baseline Hcy levels and thechanges in Hcy levels found in both the unadjusted (P<0.002) and the adjusted model (P<0.004). Strikingly, we found no significant effect modification by the MTHFR C677T polymorphism on the Hcy changes after benazepril treatment.There were also no statistically significant interactions of gene and environment factors (ie, gene-smoking and -drinking) on the changes in Hcy levelsafter benazepril treatment(P>0.05).Averages of body mass index(BMI).blood pressure,creatinine,uric acid and fasting blood glucose in both IS and HS subtypes were higher than those in control group(all P<0.05).Meanwhile, logistic regression revealed that hypertension (SBP:OR= 5.098,95%CI: 3.257～7.980; DBP:OR=3.168,95% CI:2.040-4.921), dyslipidemia (HDL-C:OR= 5.718,95% CI:2.075～15.756;).hyperuricemia (UA:OR= 2.995.95% CI: 1.550～5.787),Bean products excessive intake(OR= 11.225,95% CI:1.460～86.291) and Aquatic products excessive intake (OR=4.273,95% CI:2.010～9.081)were all risk factors for isehemic stroke.However, the risk factors of hemorrhagic stroke were hypertension (SBP:OR= 12.701,95% CI:6.372～25.319; DBP:OR= 13.386,95% CI: 6.955～25.761),hyperglycemia (OR=3.008,95% CI:1.698～5.329).Bean products excessive intake(OR= 8.393,95% CI:1.025～68.754) and Aquatic products excessive intake(OR=4.707,95% CI:2.096～10.571).Subjects carrying the MTRR A66G AG+GG genotype had a higher stroke risk than those carrying the AA genotype in both stroke subtype (IS:OR=1.716,95% CI:1.063-2.802 and HS:OR= 1.885,95% CI:1.052-3.272). Furthermore, the high order gene-gene interaction of the four SNPs werefound by GMDR (P-0.0010) in ischemic stroke group.However.the significant interactions were not found in hemorrhagic stroke group.Conclusion:Benazepril may cause an increase in plasma Hcy levels among hypertensive patients with low baseline Hey levels, while effect modification by MTHFR C677T genotypes on the changes in Hcy levels in response to benazepril was not significant among patients with essential hypertension. Hypertension,hyperlipidemia,hyperuricemia,Bean products excessive intake and Aquatic products excessive intake were the most prominent risk factors for ischemic stroke.In contrast,hypertension,hyperglycemia,Bean products excessive intake and Aquatic products excessive intake were the most pronounced risk factors for hemorrhagic stroke.The MTRR A66G genotypes independently increased ischemic and hemorrhagic stroke risks.Also,MTHTR C677T,MTHFR A1298C, MTR A2756G, MTRRA66G interactively contributed to ischemic stroke risk. |
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