Genetic factors predisposing to a chronic course of virus hepatitis and liver fibrosis

Abstract

Pharmaceutical companies and regulatory agencies are pursuing biomarkers as a means to increase the productivity of drug development. Quantifying differential levels of proteins from complex biological samples like plasma or cerebrospinal fluid is one specific approach being used to identify markers of drug action, efficacy, toxicity, etc. Academic investigators are also interested in markers that are diagnostic or prognostic of disease states. We report a comprehensive, fully automated, and label-free approach to relative protein quantification including: sample preparation, proteolytic protein digestion, LCMS/MS data acquisition, de-noising, mass and charge state estimation, chromatographic alignment, and peptide quantification via integration of extracted ion chromatograms. Additionally, we describe methods for transformation and normalization of the quantitative peptide levels in multiplexed measurements to improve precision for statistical analysis. Lastly, we outline how the described methods can be used to design and power biomarker discovery studies.

Influence of cytokine and cytokine receptor gene polymorphisms on the degree of liver damage in patients with chronic hepatitis C

“…Similarly, Bahr et al ( Bahr et al, 2003 ) found no association between the TNFA -308 SNP and liver cirrhosis in a German population. Goncharova et al ( Goncharova et al, 2008 ), on the other hand, reported a higher frequency of the TNFA -308/A allele in Russian patients with a lower stage of liver fibrosis/cirrhosis. The conflict between the results could be partially explained by ethnic differences among patients.…”

Genetic characteristics of the course of chronic hepatitis

“…This will require a search for new approaches and new fundamental research [8][9][10]. An active study of the genetic basis of predisposition to various infectious diseases has collected a sufficient amount of information indicating the importance of dysfunction of anti-inflammatory cytokines (TNF-a) and cytotoxic T-lymphocytes (CTLA-4) in the genesis of viral liver diseases [11][12][13]. The influence of genetic factors determines the immune status, in this regard, it is the immunogenetic aspects that determine the features of the development and progression of viral hepatitis [14,15].…”

Аналіз Асоціації Поліморфізму Генів Цитокінів IL-4, IL-10 І TNF З Біохімічними Й Імунологічними Показниками У Хворих На хронічний Гепатит С

“…В исследованиях ряда авторов показано, что гене-тический статус человека по полиморфным вариантам ряда генов цитокинов является важнейшим фактором, определяющим такие патогенетические признаки те-чения хронических вирусных гепатитов, как количест-венное содержание цитокинов, а также уровень биохи-мических показателей крови [12][13][14].…”