Koroner kalp hastalıklarında adducin ve Na+ - K+ATPaz gen polimorfizmi
Adducin and Na+ - K+ ATPase gene polymorphism in coronary heart disease
Yazar: NİLÜFER BOZKURT
Danışman: PROF. DR. TURGAY İSBİR
İstanbul Üniversitesi / Sağlık Bilimleri Enstitüsü / Moleküler Tıp Ana Bilim Dalı
Derece: Doktora, 2006
Konu: Moleküler Tıp = Molecular Medicine

Özet:
ÖZETBozkurt, N. Koroner Kalp Hastal klar nda Adducin ve Na- K ATPaz Gen Polimorfizmi.stanbul Üniversitesi Sa l k Bilimleri Enstitüsü, Molekuler T p ABD. Doktora Tezi. stanbul.2006.Bugüne kadar üzerinde gerek çevresel gerekse varsay lan genetik yatk nl kla ilgili pek çokçal ma yap lm olan kalp hastal klar yeni yüzy lda da toplum sa l n tehdit eden en büyüketmenlerden biri olarak yerini korumaktad r.Pek çok toplumda kardiyovasküler hastal klarayatk nl kta rol oynad dü ünülen aday genler ara t r lm ve etnik özelliklere göre farklbulgular elde edilmi tir.Bu tez çal mas nda 50 sa l kl birey ve Marmara Üniversitesi Kalp ve Damar CerrahisiAnabilim Dal nda KABC uygulanan hastalardan 65 birey üzerinde Na+ \ K+ ATP az genpolimorfizmi ve alfa Adducin gen polimorfizmi incelenmi tir.Toplam 115 örnekten elde edilen DNA lardan Na+ \ K+ ATPaz ve alfa Adducinpolimorfizmini saptamak için Polimeraz Zincirleme Reaksiyonu (Polymerase Chain Reaction,PCR), Restriksiyon Fragman Uzunluk Polimorfizmi (Restriction Fragment LengthPolymorphism, RFLP) ve agaroz jel elektroforezi teknikleri kullan lm t r.Çal mam z sonucunda, Na+-K+ATPaz A alleli ta ma aç s ndan çal ma gruplarincelendi inde A alleli ta mayan (CC genotipinin) KAH grubunda artt fakat istatistikselolarak anlaml l a ula mad , C aleli ta ma aç s ndan çal ma gruplar incelendi inde Calleli ta yan (CC+CA genotipinin)bireylerin KAH yakalanma riskinin 1,97 arttgözlenmi tir.Na+-K+ ATPaz A aleli ta yan bireylerin tamam n n dü ük kalp debisine sahip olduklarbununla birlikte CC genotipli bireylerin hiçbirinde dü ük kalp debisi bulunmad ,C allelita mayanlarda ise dü ük kalp debisi olu ma riskinin 5.71 kat artt gözlenmi tir.ntraaortik balon pompas kullan lan hastalar n hepsinin Na+-K+ ATPaz A alleli ta d klarNa+-K+ ATPaz C alleli ta mayan bireylerde ise IABP kullan m n n 4.28 kat artt tespitedilmi tir. Ölümü gerçekle en bireylerin hepsinin Na+-K+ ATPaz A alleli ta d klar ; C allelita mayan bireylerde (AA genotiplilerde) ölme riskinin 2.85 kat artt da gözlenmi tir.Alfa Adducin gen polimorfizmi incelendi inde hasta grubunda TG genotipinin (%58)kontrole göre (%26) yükseldi i ve TT genotipinin kontrole göre azald gözlemlenmi tir.Koroner arter hastalar nda Adducin G allel frekans kontrollere göre istatistiksel olarakanlaml ekilde yüksek bulunmu (p:0.000) ve koroner arter hastal na yakalanma riskinin7.5 kat artt belirlenmistir.Adducin G ta mayan (TT genotipli) bireylerde dü ük kalp debisigeli me riskinin 5 kat artt , IABP kullan m riskinin 2.5 kat artt ve ölüm varl n nistatistiksel olarak anlaml ekilde yükselmi oldu u ve ölüm riski 15 kat artt saptanm t r.Anahtar kelimeler : Na+ \ K+ ATP az gen polimorfizmi ,alfa Adducin gen polimorfizmi,Koroner arter hastal , Intraaortik balon pompasBu çal ma stanbul Üniversitesi Bilimsel Ara tirma Projeleri Birimi taraf ndanT-381/08032004 nolu proje olarak desteklemi tir.

Abstract:
ABSTRACTBozkurt, N. Adducin and Na + / K + ATPase Gene Polymorphism in Coronary Heart Disease.stanbul University, Institute of Health Science, Department of Molecular Medicine. stanbul.2006.Cardiovascular problems are grouped as one of the most important health problems all overthe world .Both genetic and environmental factors are thought to determine the outcome andstudies on many candidate genes showed that there is an outcome difference in differentethnic groups showing the importance of the genetic predisposition for these problems.Na+ \ K+ ATPase and alfa Adducin gene polymorphisms were examined in 50 control subjectsand 65 patients from Marmara University, department of Cardiovascular Surgery that haveundergone Coronary Arter bypass .Polymerase Chain Reaction (PCR) , Restriction Fragment Length Polymorphism (RFLP) ,and agarose gel electrophoresis techniques were used to determine theNa+ \ K+ ATPase and alfa adducin gene polymorphisms in totally 115 subjects.As a result of our study , when we analyzed our group according to Na+ \ K+ ATPase genecontribution to interindividual variation in Coronary artery diseases, we found that patientswith CC genotype have a higher risk for Coronary artery diseases but the difference is notstatistically significant.When the contribution of the C allele for that disease was analysed wefound that having the C allele (CC+CA) increased the risk 1.97 times.We found that all the patients with A allele have low cardiac output, no patient with CCgenotype have low cardiac output, and having a C allele reduces the risk for low cardiacoutput 5.71 times.We also found that intraaortic balloon pump was used for all patients with Na+-K+ATPase Aallele genotype and the risk for that intraaortic balloon pump increases 4.28 times for thepatients with no C allele. More over, it is shown that patients with the A allele have 100 %mortality risk and the risk increases 2.85 times for the patients wih no C allele.When we analysed our group for alpha adducin gene polymorphism, we found that TGgenotype ratio increases significantly (%58 \%26) in the patient group and TT genotypedecreases.Alpha adducin G allele frequency is shown to increase significantly in the Coronary arterydiseases group (p=0.000) and the risk for that disease is shown to increase 7.5 times.We foundthat prevalence of low cardiac output increases 5 times, usage of intraaortic balloon pumpincreases 2.5 times and the mortality risk increases 15 times in the patients with no G allele(TT genotype)Key Words: Na+ \ K+ATPase gene polymorphism, alfa Adducin gene polymorphism,Coronary artery diseases, intraaortic balloon pumpThis study was supported by the Research Support Unit of stanbul University as the Projectno T-381/08032004