Genetic polymorphisms of interleukin-1 beta in association with the development of alcoholic liver disease in Japanese patients

OBJECTIVE: Cytokine interleukin-1 beta plays a central role in the inflamma tion process. Serum levels of IL-1 beta are elevated in patients with alcoh olic liver disease (ALD), especially in those with cirrhosis and alcoholic hepatitis. Recently, the presence of genetic polymorphisms of this cytokine was confirmed. The aim of this study was to determine whether IL-1 beta po lymorphisms are associated with the development of ALD. METHODS: We examined the frequency of two polymorphisms in the IL-1 beta ge ne located in promoter -511 and exon 5 +3953 locus by restriction fragment length polymorphisms in 142 male patients with ALD, 30 heavy drinkers witho ut ALD, and 218 healthy controls. RESULTS: The carriers of -511 IL-1 beta allele 2 were present significantly more often in patients with alcoholic cirrhosis than in those with noncirr hotic ALD (p = 0.026), heavy drinkers without ALD (p = 0.001), and healthy controls (p = 0.032). The frequencies of allele 2 and heterozygotes of +395 3 polymorphism were both significantly higher in heavy drinkers without ALD than in patients with ALD (allele, p = 0.030; genotype, p = 0.027) and hea lthy controls (allele, p = 0.047; genotype, p = 0.043). The haplotype, IL-1 beta -511 allele 2/+3953 allele 1 was associated with the development of a lcoholic cirrhosis (p < 0.05). CONCLUSIONS: These results suggest that IL-1 beta polymorphisms may be rela ted to the development of ALD in Japanese alcoholics. (C) 2000 by Am. Coil. of Gastroenterology.