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The Association Between CYP4F2 Rs2108622 Loci Polymorphism And Ischemic Stroke:a Meta-analysis

Posted on:2017-03-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:C MengFull Text:PDF
GTID:1224330488451889Subject:Surgery
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Background and aimCytochromeP450 was the most important enzyme system,which was involved in the metabolism of human body. CYPs might been divided into three major groups, including 51 family(1-51). CYP4 (cytochromeP450, family 4) belonged to the third group of CYPs, mainly responsible for the metabolism of fatty acids and small amounts of xenobiotics substance. CYP4F2 (cytochromeP450, family4, subfamily F, polypeptide 2) was a human CYP4 members of the family of CYP450 gene. The gene encoded ω-hydroxylase, which was the main synthetase of converting arachidonic acid into 20-HETE. The rs2108622 loci of CYP4F2 was more involved in recent research. It was the common mutation that 1347 G mutates A, which resulted in its 433 amino acids valine (V) substituted by methionine V (V433M). CYP4F2 changes in the physiological and biochemical functions came subsequently. Recent studies had shown that the mutation in rs2108622 loci from G to A, causing the 433rd amino acid convention of valine to methionine, could reduce the 20-HETE production. As a result,the incidence of ischemic stroke decreased.Although the research about rs2108622 (V433M) loci polymorphism of CYP4F2 gene and ischemic stroke increased gradually, but the results were not consistent[12.13],which might come from small sample size, ethnic choice defect. Here, in order to increase the sample size and acquire reliable conclusion, we adopted the method of meta-analysis to comprehensively and systematically evaluate the current researches about CYP4F2 rs2108622 loci polymorphism and ischemic stroke relationship. In this case,we might define the relationship more well between the polymorphism and ischemic stoke and explain more precisely the genetic etiology of ischemic stoke.The conclusion might offer more indications in the diagnosis, treatment and prognosis of ischemic stokeMethodsRetrieving relevant documents based on English words such as "ischemic stroke" or " cerebral infarction "、" polymorphsim " or " polymorphisms "、" CYP4F2 " or " rs2108622 " or "CYP4F2V433M" from PubMed, EMbase, Web of Science; With "脑梗死", "基因多态性 ", "CYP4F2" or "rs2108622" or "CYP4F2V433M" for the search term, search the database including the Chinese full text database (CNKI), Chinese journal database CBM, ten thousand party and VIP database。It was necessary to get the full text as far as possible. Searching deadline is January 2015.Screening of literature could be conducted by two researchers independently. They carried on the quality evaluation by the way of NOS evaluation according to the inclusion criteria selection literature. NOS evaluation included a total of nine stars, and five stars or more could be considered as meeting this study. We collect the following data from the selected literatures: the first author, publication time, countries, race, the average age of sample size and the way of selecting control groups.According to the heterogeneity of forest figure,the OR value was emerged with the corresponding effect model by menas of STATA 11.0 statistical analysing software in the five kinds of genetic model,such as:allele model,A v G the dominant model AA+GA vs. GG, recessive model AA vs. GG+GA, superdominant model AA+GG Vs GA, codominant model AA vs. GG and GA vs. GG. We evaluated sensitivity analysis and publication bias with STATA 11.0 statistical analysing software. Subgroup analysis could be performed on the basis of genderResultsTotal 4 paper conformed to the requirements, including 1294 cases and 1413 controls. Because only the yellow race appeared, subgroup analysis could be conducted on the basis of genderIn the entire population, the OR values and 95% Cist were 0.94 (95% CI:0.74,1.20), 0.95 (95% CI:0.71,1.26),1.36 (95% CI:0.93,2.00),1.06 (95% CI:0.91,1.24),0.89 (95% CI: 0.54,1.47) and 0.54 (95% CI:0.82,0.82) respectively from allele model A v G, the dominant model AA+GA vs. GG, recessive model AA vs. GG+GA, superdominance model AA+GG Vs GA, codominance model AA vs. GG and GA vs. GG. All the emerged OR values and 95% CI included 1, showing no statistical significance. By gradually removing each study, the meta-analysis for rest research turned out to be still stable and reliable. Publication bias were detected in these five genetic model through begg and egger test. The P values, in turn, were 0.734 and 0.734,0.207 and 0.689,0.734 and 0.066,1.000 and 0.973,1.00 and 0.058, and 1.00 and 0.058, showing no publication bias. I n other words, in these five genetic model allele model A v G, the dominant model AA+GA vs. GG, recessive model AA vs. GG+GA, superdominance model AA+GG Vs GA, codominance model AA vs. GG and GA vs. GG,there was no correlation between gene rs2108622 loci polymorphism and ischemic stroke for entire population.In the male population, the OR values and 95% CIs were 0.66 (95%CI:0.51,0.84) 0.66 (95%CI:0.48,0.90),0.46 (95%CI:0.26,0.82)、0.41 (95%CI:0.23,0.73) respectively from allele model A v G, the dominant model AA+GA vs. GG, recessive model AA vs. GG+GA, codominance model AA vs. GG. All the emerged OR values and 95% CI were less than 1, showing statistical significance. Namely, there was correlation between gene rs2108622 loci polymorphism and ischemic stroke for male population. A allele and AA genotype were protective factor against ischemic stroke in male.In the female population, the OR values and 95% CIs were 1.30(95%CI:0.97,1.74)、 1.36 (95%CI:0.93,2.00),1.41 (95%CI:0.77,2.57),0.83 (95%CI:0.56,1.23) 1.58 (95%CI:0.84,2.98) and 1.31 (95%CI:0.87,1.97) respectively from allele model A v G, the dominant model AA+GA vs. GG, recessive model AA vs. GG+GA, superdominance model AA+GG Vs GA, codominance model AA vs. GG and GA vs. GG. All the emerged OR values and 95% CI included 1, showing no statistical significance. In these five genetic model,there was no correlation between gene rs2108622 loci polymorphism and ischemic stroke for female population.By gradually removing each study in subtype analysis, the meta-analysis for rest research turned out to be still stable and reliable. Publication bias were detected in these five genetic model through begg and egger test. The P values, in turn, were 0.734 and 0.207,0.734 and 0.689,0.734 and 0.066,1.000 and 0.973,1.00 and 0.058,0.734 and 0.876, showing no publication bias.ConclusionIn male crowd, the distribution of A allele and AA genotype in ischemic stroke patients was lower than normal people, indicating the protection against ischemic stroke. That was to say, there was significantly correlation between gene rs2108622 loci polymorphism and ischemic stroke only in male population other than in entire or female ones.
Keywords/Search Tags:ischemic stroke, CYP4F2, polymorphism Meta analysis
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