Association of genetic polymorphisms with histological grading of necroinflammation, staging of fibrosis, and liver function in Mexicans with chronic hepatitis C virus infection.
OBJECTIVE
The aim of this work was to establish an association between the single-nucleotide polymorphisms (SNPs) of TGFB1 (rs1800471), AT (rs3789679), MMP-1 (rs17886084), MMP-3 (rs35068180), and PAI-1 (rs1799889) and the histological grading of necroinflammation, staging of hepatic fibrosis, and liver function in Mexican patients with advanced liver fibrosis due to chronic hepatitis C virus infection.


METHODS
AT, MMP-1, MMP-3, and PAI-1 gene polymorphisms were analyzed by polymerase chain reaction in real time, whereas TGFB1 polymorphism was detected by polymerase chain reaction-based restriction fragment length polymorphism in 38 patients with established advanced liver fibrosis and 50 subjects from the general population. Grading of necroinflammation and staging of liver fibrosis were assessed by liver biopsy and graded according to modified histological activity index Ishak score.


RESULTS
Regarding TGFB1 SNP, significant differences were found between G/G and G/C genotypes of patients with hepatic necroinflammation (P = 0.05) and hepatic fibrosis (P = 0.002). There were also significant differences among genotypes of patients with the AT SNP in hepatic necroinflammation (P = 0.01). The albumin-globulin ratio between genotypes of patients with the MMP-3 SNP gene showed significant differences (P = 0.02).


CONCLUSIONS
Our findings demonstrate that a specific combination of genotypes associated with biochemical values and a histological high score determine more severe liver disease. The presence of the G/G genotype of TGFB1 SNP in patients was significantly associated with severity of liver necroinflammation and fibrosis. Patients with the G/G genotype of AT SNP were associated with severe necroinflammation. The albumin-globulin ratio was increased in patients with the 6A allele of MMP-3 SNP. These results might contribute to diagnosis and further establishment of liver disease treatment.
From the *Institute of Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, †Research Coordination, and ‡Research Institute of Dentistry, University Center of Health Sciences, University of Guadalajara, Jalisco, México; and §INNOVARE, Guadalajara, Jalisco, México.
María Guadalupe
MG
Sánchez-Parada
Bertha Adriana
BA
Alvarez-Rodríguez
Belinda Claudia
BC
Gómez-Meda
Rogelio
R
Troyo-Sanromán
Laura Verónica
LV
Sánchez-Orozco
Ana Lourdes
AL
Zamora-Perez
Martha Silvia Lucano
MS
Landeros
Juan
J
Armendáriz-Borunda
D000368:Aged; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008800:Mexico / Q000208:ethnology; D008875:Middle Aged; D009336:Necrosis / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012709:Serum Albumin / Q000235:genetics; D012712:Serum Globulins / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D012709:Serum Albumin; D012712:Serum Globulins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D019278:Matrix Metalloproteinase 3