POLIMORFISMELE C677T SI A1298C DIN GENA MTHFR – FACTORI DE RISC GENETICI PENTRU APARITIA PREECLAMPSIEI

POLIMORFISMELE C677T SI A1298C DIN GENA MTHFR – FACTORI DE RISC GENETICI PENTRU APARITIA PREECLAMPSIEI

Procopciuc Lucia Maria*, Caracostea Gabriela**, Zaharie Gabriela**, Popa Monica**, Puscas Mariana**, Iordache Georgiana**, Olteanu Ileana*1, Stamatian F.**

* Catedra de Biochimie, Universitatea de Medicina si Farmacie “I. Hatieganu” Cluj-Napoca
**Clinica Ginecologie I Universitatea de Medicina si Farmacie “I. Hatieganu” Cluj-Napoca

Rezumat

     Introducere: Doua polimorfisme C677T si A1298C din gena MTHFR care influenteaza concentratia 5- metiltetrahidrofolatului necesar pentru remetilarea homocisteinei (HCys), scad activitatea enzimei si pot fi implicate în aparitia preeclampsiei.

   Scop: 1. de a studia rolul acestor mutatii trombofilice în preeclampsie 2. de a examina efectul sinergic al polimorfismelor din gena MTHFR în aparitia preeclampsiei 3. de a investiga asocierea dintre genotipurile mutante si severitatea preeclampsiei
   Material si metoda: S-a determinat genotipul pentru polimorfismele C677T si A1298C la 56 femei diagnosticate cu diferite tipuri de preeclampsie si 59 subiecti de control normotensivi utilizând metoda PCR- RFLP.
   Analiza statistica: Frecventa genotipurilor în ambele grupuri a fost comparata utilizând testul Fisher. S-a calculat riscul relativ, odds ratio (OR) si intervalul de confidenta. Valorile ale lui p mai mici de 0.05 au fost considerate semnificative din punct de vedere statistic.
   Rezultate: Riscul relativ de aparitie al preeclampsiei la subiectii cu genotip CT si TT a fost de 2.51 (95I IC T1.04–6.04t, p= 0.05) si respectiv 5.09 (95I IC T1.35–19.16t, p= 0.012). Riscul relativ de aparitie al preeclampsiei la subiectii cu genotip AC si CC a fost de 2.17 (95I IC T0.94–5.02t p= 0.09) si respectiv 4.75 (95I IC T0.96–23.44t p= 0.049). Subiectii pozitivi doar pentru polimorfismele C677T si respectiv A1298C au avut un risc crescut de 2.47 (95IIC T0.91- 6.69t, p= 0.09) ori si respectiv 1.55 ori (95IIC T0.57- 4.21t, p= 0.45) de a dezvolta preeclampsia. Femeile purtatoare a ambelor polimorfisme au avut un risc de 3.85 (95IIC T1.39- 10.66t, p < 0.01) de a dezvolta preeclampsia. Femeile pozitive pentru C677T, A1298C sau cu trombofilie combinata au avut un risc crescut de aparitie a preeclampsiei forma severa (OR 5.42, 95IIC T1-29.32t, p = 0.05; OR 6.31, 95IIC T1.16- 34.26t, p = 0.044; OR 2.68, 95IIC T0.59- 12.04t, p = 0.014).
   Concluzii: Rezultatele sugereaza ipoteza ca polimorfismele C677T si A1298C din gena MTHFR pot avea un rol important în aparitia preeclampsiei în populatia studiata.

Abstract – C677T AND A1298C POLIMORPHISMS OF MTHFR GENE – RISK FACTORS FOR PREECLAMPSIA

    Background: Two common C677T and A1298C SNP-s in the MTHFR gene that affect 5-methyltetrahydrofolate required for homocysteine (Hcy) remethylation, decrease enzyme activity and could be implicated in the development of preeclampsia.
    Aim of study: 1. to investigate the implication of these thrombophilic mutations in preeclampsia 2. to examine the synergic effect of MTHFR polymorphisms in the development of preeclampsia 3. to investigate the association of the mutated genotypes with the severity of preeclampsia
    Materials and methods: C677T and A1298C polymorphisms were genotyped in 56 women diagnosed with different types of preeclampsia and 59 normotensive control subjects using PCR- RFLP analysis. Statistical analysis: The genotype frequency in both groups was compared using the Fisher exact test. Odds ratio (OR) with 95ICI was calculated. p less than 0.05 was considered statistically significant.
    Results: The relative risk for preeclampsia in subjects with the CT and TT genotype was 2.51 (95I CI T1.04–6.04t, p= 0.05) and 5.09 (95I CI T1.35–19.16t, p= 0.012), respectively. The relative risk for preeclampsia was 2.17 (95I CI T0.94–5.02t p= 0.09) and 4.75 (95I CI T0.96–23.44t p= 0.049), respectively in women carrying the 1298AC genotype CC genotype. Carriers of either the C677T or the A1298C polymorphism had a 2.47 (95ICI T0.91- 6.69t, p= 0.09)-fold and 1.55 (95ICI T0.57- 4.21t, p= 0.45)-fold, respectively, increased risk for preeclampsia. Women carrying both polymorphisms had 3.85-fold (95ICI T1.39- 10.66t, p < 0.01) increased risk for preeclampsia. Women carrying C677T, A1298C or with combined thrombophilias had higher risk for severe preeclampsia (OR 5.42, 95ICI T1-29.32t, p = 0.05; OR 6.31, 95ICI T1.16- 34.26t, p = 0.044; OR 2.68, 95ICI T0.59- 12.04t, p = 0.014).
    Conclusion: The results support the hypothesis that in the studied population the C677T and A1298C MTHFR gene polymorphisms could play a significant role in preeclampsia.
Key words: preeclampsia, C677T, A1298C, PCR-RFLP analysis