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Miomi so benigni tumorji maternice in so najpogostejši tumorji ženskih spolnih organov. So hormonsko odvisni tumorji, saj se pojavljajo le v rodnem obdobju, po menopavzi pa se njihova velikost zmanjša. Vzroki za nastanek in rast miomov so številni, vendar še ne popolnoma dokazani. Njihov pojav je odvisen od številnih interakcij med geni ter okoljem, raziskave pa so ugotovile tudi vpliv družinske predispozicije za nastanek miomov. Namen našega dela je bil ugotoviti ali so izbrani polimorfizmi v genih CYP17A1, ESR1, IL12B, IL12RB1, IL23R in PTPN22 povezani z nastankom miomov in raziskati razlike med epidemiološkimi in genetskimi dejavniki med skupinama bolnic in kontrol. Prav tako smo tudi poskušali ugotoviti ali obstajajo genetske razlike med skupinama bolnic s solitarnimi miomi ter multiplimi miomi. V študijo smo vključili 169 slovenskih bolnic z miomi in 133 zdravih posameznikov iz kontrolne skupine. Iz vzorcev krvi bolnic in zdravih kontrol, smo izolirali DNK ter izvedli genotipizacijo izbranih polimorfizmov z metodo PCR – RFLP in analizo fragmentov na agaroznem gelu. Pri primerjavi epidemioloških faktorjev med bolnicami in kontrolno skupino smo ugotovili, da lahko tveganje za nastanek multiplih miomov poveča zgodnja menarha, manjše število porodov, kajenje in pozitivna družinska anamneza. Z asociacijsko študijo smo ugotovili povezavo dveh polimorfizmov v genih CYP17A1 in IL12RB1 z boleznijo. Bolnice z multiplimi miomi so imele značilno nižji delež genotipa AA genskega polimorfizma rs743572 na genu CYP17A1 v primerjavi z zdravimi kontrolami. Genotip GG (oziroma alel G) tako predstavlja dejavnik tveganja za nastanek miomov, genotip AA pa zaščitni faktor. Pri analizi genskega polimorfizma rs11575934 na genu IL12RB1 smo prav tako ugotovili zaščitno delovanje genotipa AA pred pojavom te bolezni. Pri vseh drugih izbranih polimorfizmih značilne razlike med skupinami nismo našli. Naš rezultat nakazuje na potrebo po dodatnih raziskavah, s katerimi bi lahko polimorfizma na genih CYP17A1 in IL12RB1 potrdili kot genska označevalca za miome maternice. Analiza epidemioloških dejavnikov je pokazala na možne preventivne ukrepe, ki bi lahko ščitili pred nastankom oziroma ponovitvijo miomov maternice. S podobnimi raziskavami kot je bila naša, lahko tako prispevamo k boljšemu razumevanju te bolezni. Uterine leiomyomas are the most common benign tumors of the female genital tract. The tumors are hormone dependent, because they appear only in the fertile period and regress after the menopause. There are many factors promoting their initiation and growth, but they remain poorly understood. Their occurrence depends on a number of interactions between genes and environment and previous studies have shown that genetic predisposition is also important. The aim of this study was to determine whether selected polymorphisms in genes CYP17A1, ESR1, IL12B, IL12RB1, IL23R and PTPN22 are associated with the initiation of uterine leiomyomas and to evaluate differences in epidemiological and genetic factors between groups of controls and patients. We also investigated differences between women with solitary and multiple myomas. In our study 169 patients with leiomyomas and 133 controls were included. From the blood samples of patients and healthy controls we isolated DNA and genotyped single nucleotide polymorphisms using the PCR – RFLP method followed by agarose gel electrophoresis. The comparison of epidemiological factors in patients and controls has shown a significant statistical difference between women with multiple leiomyomas and healthy controls. This observation leads to the conclusion that the risk for the initiation of multiple myomas can be increased by an early menarche, lower number of births, smoking and positive family history regarding leiomyomas. With the association study we could determine an association of polymorphisms with the disease in genes CYP17A1 and IL12RB1. Patients with multiple myomas had a lower frequency of genotype AA in genetic polymorphism rs743572 in gene CYP17A1 in comparison to healthy controls. The genotype GG (or allele G) is therefore a risk factor for the initiation of myomas, while genotype AA is a protection factor. The analysis of the genetic polymorphism rs11575934 in gene IL12RB1 has also shown the protective effect of genotype AA prior to the occurrence of the disease. In all other selected polymorphisms differences between groups were not found. According to our result, additional research that could perhaps confirm the polymorphisms CYP17A1 and IL12RB1 as genetic markers for uterine leiomyomas would be necessary. The analysis of epidemiological factors provided data that could be helpful for determining preventive measures against this disease. With similar research projects we can contribute to a better understanding of this disease. |
