Interleukin 10 promoter haplotype is associated with alcoholic liver cirrhosis in Taiwanese patients

Abstract

Alcoholic liver cirrhosis is a severe form of alcohol-related liver damage. More than 95% of heavy drinkers develop a fatty liver, but only 35% of them develop cirrhosis. We postulate that genetic factors may play a role in this difference. Genetic polymorphisms of the cytokine genes may influence Kupffer cells cytokine genes expression. In this study, we evaluated the promoter polymorphisms of interleukin (IL) 1β, IL 6, IL 10, and tumor necrosis factor alpha (TNFα) and aimed to clarify the association between the polymorphisms and the disease. Forty alcoholic patients with liver cirrhosis and 64 healthy volunteers were included in our investigation. Genotyping on IL 1β –511 T>C, IL 6 –572 G>C, IL 10 –819 C>T, IL 10 –1082 G>A, and TNFα –308 G>A was done. Another 36 patients with recurrent alcoholic pancreatitis were included as an additional control group. Genotyping on IL 10 –819 C>T and IL 10 –1082 G>A was done. The polymorphisms on IL 1 and IL 6 showed no significant association. The p value for TNFα –308 G>A was 0.028 in comparison with healthy volunteers. Although the p value was less than 0.05, it did not reach significance after Bonferroni correction. The p values for IL 10 –819 C>T and IL 10 –1082 G>A were respectively 0.031 and 0.026 in healthy volunteers and 0.028 and 0.023 in the alcoholic pancreatitis group. The results also did not reach significance after Bonferroni correction. Among the participants with the GCC haplotype, healthy volunteers had p = 0.027 (p < 0.05) and an odds ratio (OR) of 0.124 [confidence interval (95%) CI, 0.015–0.997], whereas the alcoholic pancreatitis group had p = 0.023 (p < 0.05) and an OR of 0.106 (95% CI, 0.012–0.912). The odds ratio of people having one ATA haplotype was 6.233 (95% CI, 0.739–52.547) in healthy volunteers and 6.588 (95% CI, 0.727–59.679) in the alcoholic pancreatitis group; the corresponding rate was 10.521 (95% CI, 1.252–88.440) and 12.833 (95% CI 1.408–117.008) for people with two ATA haplotypes. The p values in these groups were 0.031 (p < 0.05) and 0.028 (p < 0.05), respectively. The presence of a GCC haplotype could have protective effect against alcoholic liver disease, whereas the presence of an ATA haplotype could predispose carriers to the disease. The IL 10 promoter haplotype is associated with alcoholic liver cirrhosis in Taiwanese patients.

Keywords

• Alcoholic liver cirrhosis
• IL 10 haplotype
• IL 10 promoter polymorphism
• TNFα promoter polymorphism