Mathematic Model for Prediction of Liver Fibrosis Progression Rate in Patients with Chronic Hepatitis C Based on Combination of Genomic Markers

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Abstract

Aim of study. To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, NOS3894, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI and their prognostic value for prediction of liver fibrosis progression rate in patients with chronic hepatitis C (CHC).

Subjects and methods: 118 patients with CHC were divided into «fast» and «slow» (fibrosis rate progression ≥0,13 and <0,13 fibrosis units/yr; n =64 and n =54) fibrosis groups. Gene polymorphisms were determined. Statistical analysis was performed using Statistica 10.

Results. A allele (p =0,012) and genotype AA (p =0,024) of AGT G-6T gene, as well as T allele (p =0,013) and MT+TT genotypes (p =0,005) of AGT 235 M/T gene were significantly more common in «fast fibrosers» than in «slow fibrosers». Patients with genotype TT of CYBA 242 C/T had a higher fibrosis progression rate than patients with CC+CT genotype (p =0,02). Our analysis showed a protective effect of TT genotype of ITGA2 807 C/T on fibrosis progression rate (p =0,03). There was a trend (p <0,15) to higher fibrosis progression rate in patients with mutant alleles and genotypes of TGFb +915 G/C, FXIII 103 G/T, PAI -675 5G/4G genes. Other gene polymorphisms were not associated with enhanced liver fibrosis. To build a mathematical model for prediction of liver fibrosis progression rate we performed coding with scores for genotypes and virus genotype. Total score correlated with the fibrosis progression rate (R =0,39, p =0,000).

Conclusion: Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.

 

About the authors

Larisa Mikhaylovna Samokhodskaia

Lomonosov Moscow State University

Email: slm@fbm.msu.ru
к.м.н., доц., Факультет фундаментальной медицины Russian Federation

Ekaterina Evgen'evna Starostina

Lomonosov Moscow State University

Author for correspondence.
Email: starostinaee@gmail.com
аспирант, Факультет фундаментальной медицины Russian Federation

Elena Borisovna Yarovaya

Lomonosov Moscow State University

Email: yarovaya@mech.math.msu.su
д.ф.-м.н., доц., Механико-математический факультет Russian Federation

Tat'yana Nikolaevna Krasnova

Lomonosov Moscow State University; Sechenov First Moscow state medical university

Email: krasnovamgu@yandex.ru
к.м.н., доц., Факультет фундаментальной медицины Russian Federation

Nikolay Alekseevich Mukhin

Lomonosov Moscow State University; Sechenov First Moscow state medical university

Email: moukhin-nephro@yandex.ru
д.м.н., проф., академик РАН, Факультет фундаментальной медицины Russian Federation

Vsevolod Arsen'evich Tkachuk

Lomonosov Moscow State University

Email: vat@fbm.msu.ru
д.б.н., проф., академик РАН, декан ФФМ МГУ Russian Federation

Viktor Antonovich Sadovnichy

Lomonosov Moscow State University

Email: info@rector.msu.ru
д.ф.-м.н., проф., академик РАН, ректор МГУ Russian Federation

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