[Mathematic Model for Prediction of Liver Fibrosis Progression Rate in Patients with Chronic Hepatitis C Based on Combination of Genomic Markers].
OBJECTIVE
To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, N0S3894, 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).


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 TTgenotype 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 modelfor prediction of liverfibrosis 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).


CONCLUSIONS
Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.
L M
LM
Samokhodskaia
E E
EE
Starostina
E B
EB
Yarovaya
T N
TN
Krasnova
N A
NA
Mukhin
V A
VA
Tkachuk
V A
VA
Sadovnichy
D000328:Adult; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D065840:Protective Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*
C056564:ITGA2B protein, human; D039421:Integrin alpha2; D016212:Transforming Growth Factor beta