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Relationship between Homocysteine, MTHFR Gene Polymorphisms and Atherosclerotic Cerebral Infarction

Author: LinXiaoHui
Tutor: LiNa；LiuJunYan
School: Hebei Medical University
Course: Neurology
Keywords: Homocysteine methylenetetrahydrofolate red- uctase Gene polymorphism Cerebral infarction Atherosclerosis
CLC: R743.3
Type: Master's thesis
Year: 2004
Downloads: 167
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Abstract


Objective:Elevated plasma homocysteine levels has been regarded as an important risk factor for atherosclerotic vascular disease.Variation in the levels of the homocysteine has been shown to be due to nutritional status and homocysteine metabolism related enzymes gene polymorphism. N5，N10-methylenetetrahydrofolate reductase(MTHFR) is one of the key enzymes that catalyzes the remethylation of homocysteine.A genetic polymorphism for the C to T substitution at nucleotide 677 of the MTHFR gene leads to a reduction in enzyme activity and subsequently mild or moderate elevation of plasma homocysteine. However,the association between another mutation causing a A-C transtitution at nucleotide 1298 and plasma homocysteine has been controversial,which has prevented a definitive conclusion to date.Many enviromental and inherited factors have been held responsible for the development of ischemic stroke.MTHFR gene has been defined as one of the important inherited predisposing factors.The roles of the C677T and A1298C mutations separated or combined in ischemic stroke have been not clear and controversial.Different subtypes of ischemic stroke <WP=7>are due to different risk factors. Elevated plasma homocysteine and MTHFR gene polymorphism may be associated with a certain subtype of stroke.The purpse of this study is to investigate the relation between plasma homocysteine , the C677T and A1298C polymorphisms of the MTHFR gene, and atherosclerotic cerebral infarction in a case-control study.Methods:68 patients were investigated with atherosclerot- ic cerebral infarction (47men, 21women and mean age,60.07 years) defined by the Chinese Fourth Cerebralvascular Disease Meeting Criteria and belong to the large-artery disease according to TOAST criteria.50 age- and sex matched persons(33men,17women and mean age,58.70 years) were made as controls.Fasting blood samples were drawn from antecubial vein for measurment of plasma glucose,lipids, plasma total homocysteine(tHcy),besides examination of C677T and A1298C polymorphisms of MTHFR gene.Concentration of tHcy was measured by fluorescence polarization immunoassa- y(FPIA). Polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP)was applied to detect C677T and A1298C gene polymorphisms.Past medical history of smoking, hypertension, diabetes and hyperlipidemia was taken from all the subjects.Results:(1)Age,sex and prevalence of smoking were no significant differences between case and control groups (P>0.05).The cases had a significantly higher prevalence of hypertension, diabetes and hyperlipidemia than did the <WP=8>controls(P<0.05).(2)Plasma total homocysteine levels was significantly higher in cases than in controls(17.91μmol/L versus 12.66μmol/L,P<0.01). (3)The distribution of C677T genotypes was significantly different between case and control groups.The frequencies of TT genotype and T allele were significantly higher in cases than in controls(36.8% versus 16.0%, P<0.01; 59.6% versus 38.0%,P<0.005,respectively).But no significant differences in 1298AC/CC genotype and C allele between the two groups were observed(26.5% versus 30.0%,P>0.05;14.7 versus 15.0%,P>0.05, respectively).(4)For the combined genotypes ,compaired with the control group,the case group had significantly higher frequency of 677TT/1298AA genotype (32.4% versus 16.0%,P<0.05) and lower frequency of 677CC/1298AA genotype(10.3% versus 26.0%,P<0.05). But there were no significant differences in the frequencies of the 677CT/1298AC,677CC/1298AC and 677CT / 1298AA genotypes between the two groups.In the case group,there were 3 cases with 677TT/1298AC genotype and 1 case with 677CT/1298CC genotype respectively,but no one carried any one of the two genotypes in controls. In addition,no one carring the homozygocity for the two mutations (677TT/1298CC) was observed.(5) The tHcy concentration was significantly higher in TT genotype than CT and CC genotypes both in csase(27.36μmol/L versus 14.17μmol/L,P<0.05; 27.36μmol/L versus 13.57μmol/L,P<0.05,respectively) and in controls(18.14μmol/

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Cerebrovascular disease > Acute cerebrovascular disease ( stroke)
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