Influence of transforming growth factor-beta1 gene polymorphism at codon 10 on the development of cirrhosis in chronic hepatitis B virus carriers

Abstract

Transforming growth factor (TGF)-beta1 is a key cytokine producing extracellular matrix. We evaluated the effect of TGF-beta1 gene polymorphism at codon 10 on the development of cirrhosis in patients with chronic hepatitis B. One hundred seventy eight patients with chronic hepatitis (CH, n=57) or liver cirrhosis (LC, n=121), who had HBsAg and were over 50 yr old, were enrolled. The genotypes were determined by single strand conformation polymorphism. There were no significant differences in age and sex ratio between CH and LC groups. HBeAg positivity and detection rate of HBV DNA were higher in LC than in CH groups (P=0.055 and P=0.003, respectively). There were three types of TGF-beta1 gene polymorphism at codon 10: proline homozygous (P/P), proline/leucine heterozygous (P/L), and leucine homozygous (L/L) genotype. In CH group, the proportions of P/P, P/L, and L/L genotype were 32%, 51%, and 17%, respectively. In LC group, the proportions of those genotypes were 20%, 47%, and 33%, respectively. The L/L genotype was presented more frequently in LC than in CH groups (P=0.017). Multivariate logistic regression analysis confirms that detectable HBV DNA (odds ratio [OR]: 3.037, 95% confidence interval [CI]: 1.504-6.133, P=0.002) and L/L genotype (OR: 3.408, 95% CI: 1.279-9.085, P=0.014) are risk factors for cirrhosis.

Keywords: Hepatitis B Virus; Liver Cirrhosis; Polymorphism; Transforming Growth Factor beta1.

Fig. 1

The results of single stranded conformational polymorphism (SSCP) according to genotypes at codon 10 in transforming growth factor (TGF)-β1 gene. There were 3 different patterns: 2 bands, proline homozygous (P/P) genotype; 3 bands, proline/leucine heterozygous (P/L) genotype; and 1 band, leucine homozygous (L/L) genotype. The size of amplified single DNA band was 170 bases. The SSCP results were 100% concordant with the results of DNA sequencing.

Fig. 2

The genotype distribution at codon 10 in chronic hepatitis (CH) and liver cirrhosis (LC) groups. In the CH group, the proportions of proline homozygous (P/P), proline/leucine heterozygous (P/L), and leucine homozygous (L/L) genotypes were 32%, 51%, and 17%, respectively. In the LC group, the proportions of P/P, P/L, and L/L genotypes were 20%, 47%, and 33%, respectively. The proportion of L/L genotype in LC group was higher than that in CH group (P=0.017).