Association On SNPs Of ALOX5AP Gene And Polymorphism Of HLA-DRB In Cerebral Infarction

Cerebrovascular disease(CVD) is common and occurs frequently,which hazards human health greatly. Acute Cerebrovascular disease incidence,death rate and disablement rate are every high and it is one of the three greatreasons caused people to dead. On the clinic, the incidence of CI takes up70%-80% of that of Cerebrovascular disease. It is rising with people's age, sothe prevention and cure of CI are especially important. However, its etiologyand mechanism are still unclear. In the genealogy of this disease, theinclination of high incidence hints that genetic factor plays an important rolein the occurrence and development of this disease. In recent years, with theaccomplishment of human genome plans and the progress of investigatingtechnique of molecule biology and molecule genetics, researchers canexpediently find susceptibility genes from gene level, and provide powerfulresearch methods for the exploration of the pathogen and mechanism of thedisease.People have made a lot of researches from different parts about thequestion of Polymorphism of cerebral infarction gene. For a long period oftime, people have known few function of main susceptibility genes, and havenot be able to confirm the fatal location. Recent researches show that somepositive chainable areas have been found in the investigation of genomic scanof Cardiovascular disease, stroke and they are defined as 13p12-13 section.Their repeatability is perfect and correlate with former results. However, atpresent, there is no such report in China, we choose the five SNPs asinspective target correlated with CI in 13p12-13 section, and test DNAsequencing of the aimed segment by adopting the sanger's method , thenanalyzes the research results about CI of the Han nationality in north Chinaon above-mentioned genetic location.Many researchers think that early pathology physiological change ofatherosclerosis is the inflammation transformation;every period ofpathological changes of lymphocyte has different degree of expression andHLA-DR abnormal expression, so here we take HLA as cut-in spot, andexamine 25 HLA-DRB allele among above-mentioned same throng, aiming tofurther confirm the effect on the occurrence of atherosclerosis byinflammation mechanism.All research objects are the Han nationality in north China who have threegenerations live there, there are no blood relationship among tested people incases and controls, two group mutually match on sex and age. CI patients arediagnosed according to the forth national cerebrovascular diagnose standard.Case group: the patients are all CI ones, altogether 29 ones, among them, thereare 16 males and 13 females, their average age is 52.51±17.02. Relative group:first class relative of CI altogether are 47 ones, including six CI patients,26males, 21 females, their average age is 44.21± 14.41. Control group: , altogether41 ones, health individual without genetic disease history and Relative relation,requiring within their three generations having no atherosclerosispatients(including cerebral hemorrhage, Control group and Case group arematched on their sex and age, the record of comparison group includes gender,date of birth, native place, body height and weight, heart rate, breath, usemedicine history, there are 41 ones, including 21 males, 20 females, theiraverage age is 48.25±16.02.Adopting the case comparison analysis method, we test DNA sequencingwith sanger's in cases, first class relatives and controls for analyze SNPspolymorphism on ALOX5AP gene and HLA-DRB genetic polymorphism of theHan nationality in northern china. Then, we calculate relative risk , χ2 checkoutby adopting SPSS13.0 statistical software and examine the related data withFisher's precise probabilistic methods.Result :The reseach indicate results of the five SNPs on ALOX5AP gene inthree groups:① The research show that the appearance frequencySG13S100(A/G) of ALOX5AP gene in cases were evident higher than controls .through the checkout of statistics, χ2= 3.542,P<0.05. ② The appearancefrequency of SG13S114 (A/T) and SG13S32(A/C) on ALOX5AP gene in caseswere evident higher than controls , but have no signifficant. ③ The appearancefrequency of SG13S100(A/G) in relatives were higher than controls, althoughthere are some differences, P which has no static sense (P= 0.06). ④ There isno obvious difference between cases and first class relatives in the five SNPs.⑤ Difference of distribution of SG13S100 among male and female in casesare remarkable, that of the male patients are higher than the one of the femalepatients.. The reseach indicate results of HLA-DRB in three groups: ① The relativerisk of HLA-DRB1*04, HLA-DRB1*03(17) of cases is higher thancontrols , through the checkout of χ2 and P Accurate probability, thefrequency difference between them is significant (P<0.05).. ② The relativerisk of DRB1*12 in cases is lower than controls , through the checkout of χ2and P Accurate probability, the difference is obvious significantly((P<0.01), theother location of HLA-DRB has no significantly difference. ③ The rate ofrelative risk DRB1*04, HLA-DRB1*03(17) in first class relatives is evidenthigher than the controls, through the checkout of χ2 and P Accurate probability,the difference is significant(P <0.05) ④ The relat-ive risk of DRB1*12and DRB4*01 in first class relatives is lower than controls , through thecheckout of χ2 and P Accurate probability, the difference is obvioussignificantly(P<0.01). There is no evident difference in other allele ofHLA-DRB.⑤ There is no evident difference frequency of HLA-DRB allele incases and first class relatives .From above, we think that SG13S100(A/G) may be independencedangerous factor of CI's male in the Han nationality of northern china onALOX5AP gene. The other alleles are no assotiation each other. The resultsindicate that aberrance of SG13S100 may change the activation of FLAP, solead to atherosclerosis and inflammation. Because former research manifeststhat the relationship between HLA and disease is always genetic evidence and isnot directly with the result of disease, so HLA-DRB1*04 and DRB03*(17)maybe the sensitive gene of CI of the Han nationality in northern china, DRB1*12,DRB3*(52)01 may be protective gene of the Han nationality in northern china,we will make further research about the metabolize change of geneticproduction to confirm its the effect of mechanism...