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ID naloge: 15 Letnik: 1997 Predmet: interna medicina
Vpliv polimorfizmov v genih za alfa in beta fibrinogen na nivo fibrinogena v plazmi
Avtor: Lili Steblovnik
Mentor: doc. dr. Borut Peterlin, dr. Med
Somentor: viš. znan. sod. dr. Mojca Stegnar, dipl. biol.
IZHODIŠCA: Zvišana koncentracija fibrinogena v plazmi je dejavnik tveganja za srcno-žilne bolezni. Na koncentracijo fibrinogena v plazmi vplivajo poleg starosti, sladkorne bolezni, arterijske hipertenzije, kajenja in zvišane koncentracije holesterola v plazmi tudi genetski dejavniki. Raziskave o vplivu polimorfizmov Taql, HaeIII in BcII v genih za fibrinogen na koncentracijo fibrinogena v plazmi so pokazale nasprotujoce si rezultate.
NAMEN: Preveriti smo želeli hipotezo, da polimorfizmi TagI, HaeIII in Bcd v genih za fibrinogen vplivajo na koncentracijo fibrinogena v plazmi pri zdravih prebivalcih Slovenije.
METODE: V presecno raziskavo smo vkljucili 143 zdravih prostovoljcev, 57 kadilcev in 86 nekadilcev. V vzorcih krvne plazme smo s koagulacijsko metodo dolocili koncentracijo fibrinogena. Z metodo verižne polimerazne reakcije in s cepljenjem z restrikcijskimi encimi Tagl, HaeIII in Bcd smo v vzorcih izolirane DNK dolocili polimorfizme. Podatke smo statisticno obdelali s Studentovim t-testom, analizo variance, testom hi-kvadrat in multiplo regresijo. Vrednost p < 0,05 smo upoštevali kot statisticno znacilno.
REZULTATI: Frekvence alelov polimorfizma TaqI so bile 0,73 za alel Tl in 0,27 za alel T2, polimorfizma HaeIII 0,74 za alel G in 0,26 za alel A in polimorfizma BcII 0,78 za alel B 1 in 0,22 za alel B2. Povprecna koncentracija fibrinogena v vzorcu je bila 2,78 g/1 (95 % interval zaupanja 2,65 - 2,92 g/I), pri kadilcih višja kot pri nekadilcih (statisticno nepomembno; p = 0,40). Povezanosti polimorfizma Taql in koncentracije fibrinogena v plazmi nismo ugotovili. Na koncentracijo fibrinogena v plazmi sta pomembno vplivala polimorfizma HaeIII (p = 0,04) in Bcll (p=0,04) pri nekadilcih. Polimorfizem HaeIII je prispeval 5 % variance fibrinogena (p = 0,03). Pri kadilcih vpliv polimorfizmov HaeIII in BcII na koncentracijo fibrinogena ni bil statisticno pomemben.
ZAKLJUCKI: Ugotovili smo, da polimorfizma HaeIII in BcII pomembno vplivata na koncentracijo fibrinogena v plazmi pri zdravih prebivalcih Slovenije, ki ne kadijo. Polimorfizem TaqI ne vpliva pomembno na koncentracijo fibrinogena pri zdravih prebivalcih Slovenije.
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[Abstract / English version]
The influence of alpha and beta fibrinogen genes polymorphisms on plasma fibrinogen level
Author: Lili Steblovnik
Mentor: doc. dr. Borut Peterlin, dr. Med
Co-mentor: viš. znan. sod. dr. Mojca Stegnar, dipl. biol.
BACKGROUND: Elevated plasma fibrinogen concentration is a risk factor for cardiovascular diseases. In addition to several factors such as advanced age, diabetes mellitus, cardiovascular diseases, elevated plasma cholesterol and glucose and smoking, also genetic factors have been shown to influence plasma fibrinogen level. Studies on influence of Taql, HaeIII and Bcd polymorphisms on plasma fibrinogen concentration have shown contradictory results. Therefore, the influence of Tagl, HaeIII and Bcll polymorphisms on plasma fibrinogen concentration was investigated in healthy subjects from Slovenia.
METHODS: 143 healthy volunteers, 57 smokers and 86 non-smokers, were included in the cross-sectional study. Fibrinogen values were determined with a clotting assay. Polymorphisms were detected by polymerase chain reaction and digestion with Taql, HaeIII and BcII restriction enzymes. Statistical analysis was performed with Student's t-test, analysis of variance, chi-squared test and multiple regression analysis. A p value of < 0.05 was taken as statistically significant.
RESULTS: Frequencies for the rare alleles were for TaqI polymorphism 0.27 (allele T2), for HaeIII polymorphism 0.26 (allele A) and for BcII polymorphism 0.22 (allele B2). In all individuals mean plasma fibrinogen concentration was 2.78 g/1 (95 % confidence interval 265 - 2.92 g/1), in smokers higher than in non-smokers (not significant; p = 0.40). Polymorphism Taql was not associated with plasma fibrinogen level. There was a significant association between plasma fibrinogen concentration and HaeIII (p = 0.04) and Bcd (p = 0.04) polymorphisms in the group of non-smokers. 5 % of the plasma fibrinogen variance in non-smokers could be attributed to the HaeIII polymorphism (p = 0.03). In smokers, there was no association between HaeIII and BcII polymorphisms and plasma fibrinogen level.
CONCLUSIONS: HaeIII and BcII polymorphisms are associated with differences in plasma fibrinogen levels in healthy non-smokers from Slovenia. Polymorphism Taql has no influence on plasma fibrinogen levels in healthy subjects from Slovenia.
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