Association of Genetic Polymorphisms With Histological Grading of Necroinflammation, Staging of Fibrosis, and Liver Function in Mexicans With Chronic Hepatitis C Virus Infection

作者：Guadalupe Sanchez Parada Maria; Adriana Alvarez Rodriguez Bertha; Claudia Gomez Meda Belinda; Troyo Sanroman Rogelio; Veronica Sanchez Orozco Laura; Lourdes Zamora Perez Ana; Lucano Landeros Martha Silvia; Armendariz Borunda Juan^*

来源：Journal of Investigative Medicine, 2013, 61(7): 1088-1096.

• TGFB1
• angiotensinogen
• matrix metalloproteinases
• PAI-1
• fibrosis

Background/Aim: 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 reactionYbased 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).
Conclusion: 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 albuminglobulin 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.

• 出版日期2013-10