Correlation of polymorphism in the interleukin-1 receptor antagonist gene intron 2 with alcoholic liver disease.
BACKGROUND
Interleukin-1 receptor antagonist (IL-1ra) can inhibit the pro-inflammatory effects of IL-1, which recently has been thought to involve the pathogenesis of alcoholic liver disease (ALD). This study was undertaken to determine whether there is any association between IL-1ra gene polymorphism and ALD in a Chinese population.


METHODS
The polymorphism of IL-1ra gene intron 2 (VNTR) was assessed in 165 alcoholics (43 alcohol-dependent subjects without liver diseases, 30 patients with alcoholic fatty liver, 61 patients with alcoholic hepatitis and 31 patients with alcoholic cirrhosis) and 65 healthy control subjects by PCR with DNA of peripheral blood mononuclear cells.


RESULTS
The rate of IL-1RN*1 carriage was statistically higher in the alcoholics than in the control group (98.79% vs 93.85%, chi2=4.48, P<0.050). And the IL-1RN*1 allele frequency was more common in the alcoholics than in the control group (86.67% vs 76.92%, chi2=6.56, P<0.025). IL-1RN*1 heterozygote was significantly more frequent in the patients with alcoholic hepatitis or those with cirrhosis than in the alcohol-dependent subjects without liver diseases (32.79%, 29.03% vs 9.30%; chi2=7.84, chi2=4.84; P<0.010, P<0.050). The IL-1RN*2 allele frequency in the patients with alcoholic hepatitis and the patients with cirrhosis was also significantly higher than in those alcoholics without liver diseases (13.93%, 17.74% vs 4.65%; chi2=4.79, chi2=6.78; P<0.050, P<0.010). But the frequencies of IL-1RN*1 heterozygote and IL-1RN*2 allele appear to be not different between the patients with alcoholic fatty liver and the alcoholics without liver diseases.


CONCLUSIONS
IL-1ra gene polymorphism is closely associated with race. IL-1RN*2 allele doesn't influence the susceptibility to ALD, but the gene carriers with ALD have additional risk for aggravation of the illness.
Chen
Wei-Xing
WX
Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Xu
Gen-Yun
GY
Yu
Chao-Hui
CH
Wang
Ping
P
Yu
Min
M
Xu
Ping
P
Liu
You-Shi
YS
Li
You-Ming
YM
D000328:Adult; D017677:Age Distribution; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007438:Introns / Q000235:genetics*; D008108:Liver Diseases, Alcoholic / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011336:Probability; D017472:Receptors, Interleukin-1 / Q000235:genetics; D012016:Reference Values; D012680:Sensitivity and Specificity; D017678:Sex Distribution
D017472:Receptors, Interleukin-1