[Association between angiotensin-converting enzyme and polymorphisms of N5, N10-methylenetetrahydrofolic acid reductase gene in patients with ischemic stroke].

OBJECTIVE: To explore the association between angiotensin-converting enzyme (ACE) and the polymorphisms of N5, N10-methylenetetrahydrofolic acid reductase (MTHFR) gene in patients with ischemic stroke (IS). METHODS: Totally 454 patients with IS (IS group) and 334 controls (control group) were recruited in our study. Their I/D polymorphisms of ACE gene and C677T polymorphisms of MTHFR gene were detected by PCR and denaturing high performance liquid chromatography. RESULTS: The frequencies of DD, ID, II and CC, CT, TT genotype in IS group were 22.5%, 43.4%, 34.1%, and 51.8%, 40.5%, 7.7%, respectively, and were 17.4%, 45.5%, 37.1% and 56.9%, 38.3%, 4.8% in the control group, respectively. DD genotype was associated with large-artery atherosclerosis (LAA), and TT genotype and T allele were associated with LAA and cardioembolism. Synergistic effects were found between TT and DD/ID DD genotypes in the pathogenesis of ischemic stroke. CONCLUSION: DD, TT genotype and T allele are risk factors of IS, and ACE gene and MTHFR gene have synergistic effects in the pathogenesis of IS.

[Relationship between angiotensin converting enzyme gene and ischemic stroke].

OBJECTIVE: To study relationship between angiotensin converting enzyme (ACE) gene and ischemic stroke (IS). METHODS: (1)Four hundred and fifty-four patients and 334 controls were recruited in our study, their I/D polymorphisms of ACE gene were detected by polymerase chain reaction (PCR) and denaturing high performance liquid chromatogram, and their risk factors of IS were recorded at the same time. (2)In addition, 29 stroke-prone spontaneously hypertensive rats (SHR-SP) and 40 Sprague-Dawley (SD) rats were enrolled, and hypoxia- apnoea animal models and simple apnoea animal models were used at the same time. Their plasma angiotensin II (Ang II) levels were determined. RESULTS: The frequencies of DD, ID and II genotype in IS patients were 22.5%, 43.4% and 34.1%, respectively, and 17.4%, 45.5% and 37.1%, respectively in controls. DD genotype was associated with large artery arteriosclerosis (LAA). Plasma Ang II level in SHR-SP group was (164.49+/-34.58) ng/L, and it was higher than that in control group [(150.92+/-24.92)ng/L] with no significant difference (P>0.05). Ang II levels in apnoea and hypoxia-apnoea group were (382.84+/-62.75) ng/L and (295.90+/-55.07) ng/L, respectively, and they were significantly higher than that in control group (all P<0.01). The relative risks of DD genotype and D alleles in IS patients with smoking, alcohol abuse, or with diabetes mellitus were higher than those in controls, but II genotype and I alleles were lower than those in controls. CONCLUSION: DD genotype is a risk factor for IS, Ang II takes part in the course of hypoxia-stress, and it is correlated with smoking, alcohol abuse and diabetes mellitus in the pathogenesis of IS.

[Relationship between methylenetrahydrofolate reductase gene and ischemic stroke].

OBJECTIVE: To study the relationship between methylenetrahydrofolate reductase (MTHFR) gene and ischemic stroke. METHODS: Four hundred and fifty four ischemic stroke patients were enrolled in the study. They were divided into large artery atherosclerosis (LAA), cardioembolism (CE), small artery occlusion (SAA), stroke of other determined etiology (SOE) and stroke of undetermined etiology (SUE) according to TOAST (Trail of ORG 10172 in Acute Stroke Treatment) criteria; and they were divided into mild, moderate and severe types ischemic stroke according to their scores of neurologic impairment. Three hundred and thirty four subjects, in whom hypertension, coronary heart disease, cerebral vascular disease, diabetes mellitus, cancer, renal failure etc. were excluded, served as controls in the study. Their C677T polymorphisms of MTHFR gene were determined with polymerase chain reaction (PCR) and denaturing high performance liquid chromatography (DHPLC), and their risk factors of ischemic stroke were recorded at the same time. RESULTS: The frequencies of CC, CT and TT genotype in ischemic stroke were 51.8%, 40.5% and 7.7%, respectively, and they were 56.9%, 38.3% and 4.8% respectively in controls. TT genotype and T allele were associated with LAA and CE, moderate type and severe type of ischemic stroke. The frequencies of TT genotype and T allele in ischemic stroke patients were significantly higher in those with smoking, alcohol abuse or diabetes mellitus than those in controls (all P<0.10), but CC genotype and C allele were significantly lower in them than those in controls (all P<0.05). On the other hand, all of genotypes and alleles in ischemic stroke patients with no history of smoking, alcohol abuse or diabetes mellitus were not significantly different from those in controls. CONCLUSION: TT genotype and T allele are risk factors for ischemic stroke. It exists interactions between smoking, alcohol abuse, diabetes mellitus and MTHFR gene in the pathogenesis of ischemic stroke.

[Detecting the polymorphism of methylenetetrahydrofolate reductase gene by denaturing high performance liquid chromatography].

OBJECTIVE: To establish a method for detecting the polymorphism of methylenetetrahydrofolate reductase gene (MTHFR). METHODS: The MTHFR was amplified, and the amplified products were detected by denaturing high performance liquid chromatography (DHPLC), and the amplified MTHFR was confirmed by sequencing and restriction enzyme digesting. RESULTS: A total of 334 individuals of Han people in southern China were recruited in our study, and their polymorphisms of MTHFR were detected. The accurate rate of the DHPLC method, that was very sensitive with 100% detection rate available, was over 99%. The frequencies of CC, CT and TT genotypes were 56.9%, 38.3% and 4.8% individually, and the frequencies of T and C alleles were 23.95% and 76.05% individually. CONCLUSION: The DHPLC method can detect polymorphism of MTHFR rapidly, effectively and economically. And there is the existence of different MTHFR polymorphisms in area and race.

[Polymorphisms of ACE-1 and MTHFR genes and genetic susceptibility of ischemic stroke].

OBJECTIVE: To study the relationships between polymorphisms of angiotensin-converting enzyme 1 (ACE-1) gene and N(5),N(10) -methylene-tetra-hydrofolic acid reductase (MTHFR) gene and ischemic stroke (IS). METHODS: The polymorphisms of ACE-1 and MTHFR genes in the peripheral white blood cells of 143 patients with IS and 154 controls were analyzed using PCR- RFLP. RESULTS: The frequencies of II, ID, and DD genotypes of ACE-1 gene were 37.1%, 48.3%, and 14.7% respectively in IS patients,and were 44.2%, 37.7%, and 18.2% respectively in the controls. The relative risk of stroke in IS group was 1.2 times that in the control group. The frequencies of TT, CT, and CC genotypes of MTHFR gene were 14.0%; 45.5%, and 40.5% respectively in the IS group, and 5.2%, 31.8%, and 63.0% respectively in the control group. The frequency of TT genotype was 5.2% in the control group and 1.4% in the IS group (P < 0.05). The frequency of T allele was 21.10% in the control group and 36.65% in the IS group (P < 0.01). The individuals with TT + ID or CT + ID were more susceptible to IS. The individuals with TT + ID were 4.3 times susceptible to IS than the controls, and the individuals with CT + ID were 1.63 times susceptible to IS than the controls. However, the individuals with CC + ID were less susceptable to IS in comparison to the controls (P = 0.003). CONCLUSION: TT and CT genotypes of MTHFR gene may be the risk factors of IS. There is a co-effective action between polymorphisms of ACE-1 gene and those of MTHFR gene in the pathogenesis of IS. CC genotype may have a protective effect against IS.