| Objective：To investigate the relationship between the plasma homocysteine (Hcy) level andthe polymorphisms of Methylenetetraphydrofolate ruductase (MTHFR) C677T, themethionine synthase(MS) A2756G and the cystathionineβ-synthase (CBS)844ins68and their correlation with cerebral infarction in Henan Han population, to illustratethe effect of genetic mutation of MTHFR C677T,MS A2756G, and CBS844ins68onplasma Hcy level, and further to determine the importance of genetic factors inhyperhomocysteinemia (HHcy) and cerebral infarction(CI).Methods：300cases with cerebral infarction as patient group, and261healthy subjects ascontrol group (age and gender matched with patient group) were selected, all of themwere Han Population of Henan province. After questionnaire and physicalexamination, we tested the plasma Hcy level with enzymatic cycling method,extracted the genome DNA of peripheral leukocytes with phenol-chloroform kit, anddetected the gene polymorphisms of MTHFR C677T, MS A2756G, and CBS844ins68by Polymerase chain reaction (PCR) or Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) method, and sequenced.we analysed the frequency of genotype and allelic genes of both groups compared theplasma Hcy level and cerebral infarction incidences in cases with differentpolymorphic sites of the aboves genotype, all of the data were analyzed by SPSS17.0statistic software.Results：1.The mean plasma Hcy level was significantly higher in the patient groupcompared with that in the control group (19.3±7.2vs15.1±4.9) umol/L (P<0.01).Through the gender stratification，plasma Hcy levels of both male and the femalesubjects was significantly higher in the patients than that of control group (P<0.01).We failed to find any significantly differences between the stroke subtypes(P>0.05)．Correlation analysis revealed that plasma Hcy levels was related tocerebral infarction occuence in Chinese Han Population of Henan（r=0.39, P<0.001).The Multiple stepwise logistic regression analysis showed that HHcy was aindipendent risk factor of cerebral infarction in Chinese Han Population of Henanand(OR=1.156,95%CI1.105-1.209,P<0.01).2. The distribution frequency of3MTHFR C677T genotypes in patient groupswas significantly different from controls (P<0.01). The frequency of CT and TTgenotypes was remarkably higher in the patient group than that in the control group(31.6vs17.2P<0.01, and44.7vs42.2P<0.01). The TT genotype and CT genotypewere positively associated with cerebral infarction (TT: OR=3.152,95%CI:1.98-5.017and CT: OR=1.819,95%CI:1.228-2.692). The frequency of MTHFR Talleles was higher in patients than controls (OR1.89,95%CI:1.489-2.399). Theplasma homocysteine level in MTHFR C677T homozygote or heterozygote mutationwas significantly higher than that in wild type (P<0.01), especially homozygote. Thecorrelation analysis demonstrated that the polymorphism of MTHFR C677T wasrelated to occurrence of cerebral infarction (r=0.22, P<0.001). The Multiple stepwiselogistic regression analysis after adjusting the conventional risk factors showed thatMTHFR C677T gene mutations were independent risks of cerebral infarction inChinese Han population in Henan Province（OR=1.578,95%CI1.013-2.457,P<0.05). 3. The distribution frequency of3MSA2756G genotypes was not statisticallydifferent in patient group and that in controls (P>0.05). The frequency of MSA2756Ggene AA, AG, and GG genotypes was respectively84.6%,14.3%, and1%in thepatient group, while84.3%,15.7%and0%in the control group. Genotype odds ratioof genotype AG was0.908(95%CI:0.571-1.445), and that of genotype GC was0.988(95%CI:0.975-1.002).The frequency of MSA2756G G alleles in the patients andcontrols was8.2%and7.9%respectively. There was also no difference between twogroups (OR=1.043,95%CI:0.677-1.608,P>0.05,). The plasma homocysteine levelscorresponding to the3genotypes of MSA2756G were (AA,17.6±6.7),(AG,16.2±5.5), and (GG,20.0±5.9) umol/L respectively, correlation analysis demonstratedthat the genetic polymorphism of MSA2756G was not related to plasma Hcy level(r=0.036, P>0.05)and the occurrence of cerebral infarction (r=-0.003,P>0.05).Afteradjusting the conventional risk factors, the multiple stepwise logistic regressionanalysis showed that MSA2756G gene mutations were not significantly associatedwith cerebral infarction occurence.4. Two CBS844ins68genotypes were found in Chinese Han population ofHenan Province: DD and ID genotype,while II genotype was not found both patientsand controls.The frequency of DD and ID genotypes was respectively98.7%and1.3%in the patient group, while97.7%,62.3%in controls, no statistical difference ofthe distribution frequency was observed in two groups (P>0.05). There was nosignificantly difference of plasma Hcy levels between the two CBS844ins68genotypes in patient group and controls (P>0.05). Genotype odds ratio of IDgenotype was0.574(95%CI为0.160-2.058). The frequency of I alleles in bothgenotype groups was0.7%and1.1%, there was no significantly difference betweenthe two groups. The plasma Hcy level corresponding to the DD and ID genotypes was17.3±6.4umol/L and20.0±13.4umol/L respectively, there was no significantlydifference between the two genotype groups(P>0.05). Correlation analysis revealedthat CBS844ins68polymorphisms was not related to plasma homocysteine levels(r=0.21, P>0.05) and the occurrence of cerebral infarction (r=0.22, P>0.05). Afteradjusted by the conventional risk factors, the multiple stepwise logistic regressionanalysis showed that CBS844ins68gene mutations didn’t enhance the cerebral infarction risk.Conclusions:1. Plasma homocysteine levels were related to cerebral infarction occurence inChinese Han population of Henan Province. HHcy was a independent risk factor ofcerebral infarction of Chinese Han population in Henan Province.2. MTHFR C677T gene mutations could lead to HHcy, and positively related tocerebral infarction. MTHFR C677T gene mutations were perhaps genetic risk factorof cerebral infarction of Chinese Han population in Henan Province.3. MS A2756G gene mutations were not related to plasma Hcy level, and not tocerebral infarction. The MS A2756G genetic polymorphism probably was not geneticrisk of cerebral infarction of Chinese Han population in Henan Province.4. CBS844ins68gene mutations were not related to plasma Hcy level, and notto cerebral infarction. The CBS844ins68genetic polymorphism probably was notgenetic risk of cerebral infarction of Chinese Han population in Henan Province. |
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