Endothelial dysfunction gene polymorphisms and the rate of liver fibrosis in chronic hepatitis C


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Abstract

AIM: To assess the association of the CYBA, NOS3, and MTHFR gene polymorphisms and a rate of fibrosis progression in chronic hepatitis C (CHC)/MATERIAL AND METHODS: One hundred and nine CHC patients with the verified stage of liver fibrosis and cirrhosis at its onset were examined. The disease duration was determined in all the patients and additional risk factors of liver lesion were absent. A group of rapidly progressive fibrosis comprised 55 patients with a calculated fibrosis progression rate of 0.130 fibrosis units/year or higher and 54 patients with a progression rate of less than 0.130 fibrosis units/year were assigned to a slow fibrosis group. A compression group consisted of 299 healthy blood donors. The polymorphism of the genes under study was determined by polymerase chain reaction-restriction fragment length polymorphism analysis/RESULTS: The mutant TT genotype of the CYBA gene was significantly more common in the CHC patients with rapidly progressive fibrosis than in those with slowly progressive fibrosis (odds ratio for TT 9.09 at 95% confidence interval, 1.09 to 74.83; p=0.0161). No significant differences were found in the distribution of the alleles and genotypes of the NOS3 and MTHFR genes between the groups of patients with slowly and rapidly progressive fibrosis/CONCLUSION: The findings make it possible to regard the TT genotype of the CYBA gene from the C242T locus as profibrogenic and as one of the markers of the poor course of CHC.

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Полиморфизм генов дисфункции эндотелия и скорость прогрессирования фиброза печени при хроническом гепатите С. - Резюме. Цель исследования. Оценить взаимосвязь полиморфизма генов CYBA, NOS3 и MTHFR и скорости прогрессирования фиброза при хроническом гепатите С (ХГС). Материалы и методы. Обследовали 109 больных ХГС с установленной стадией фиброза и циррозом печени в его исходе. У всех пациентов определена длительность заболевания и отсутствовали дополнительные факторы поражения печени. Группу с быстро прогрессирующим фиброзом составили 55 больных с расчетной скоростью прогрессирования фиброза 0,130 ед. фиброза/год и выше, а 54 пациента с темпом прогрессирования менее 0,130 ед. фиброза/год отнесены в группу с "медленным фиброзом". Группой сравнения служили 299 здоровых доноров крови. Полиморфизм исследуемых генов определяли методом оценки длины рестриктных фрагментов продуктов полимеразной цепной реакции. Результаты. У больных ХГС с быстрым прогрессированием фиброза достоверно чаще встречался мутантный генотип ТТ гена CYBA по сравнению с группой с медленно прогрессирующим фиброзом (отношение шансов для TT=9,09 при 95% доверительном интервале от 1,09 до 74,83; p=0,0161). Не выявлено достоверных различий по распределению аллелей и генотипов генов NOS3 и MTHFR между группами больных ХГС с медленно- и с быстропрогрессирующим фиброзом. Заключение. Полученные результаты позволяют рассматривать генотип ТТ гена CYBA по локусу C242T как профиброгенный и считать его одним из маркеров неблагоприятного течения ХГС.
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