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Polymorphisms of the IL‐1 Gene Complex Are Associated With Alcohol Dependence in Spanish Caucasians: Data From an Association Study
Author(s) -
Saiz Pilar A.,
GarciaPortilla Maria P.,
Florez Gerardo,
Corcoran Paul,
Arango Celso,
Morales Blanca,
Leza Juan C.,
Alvarez Sandra,
Díaz Eva M.,
Alvarez Victoria,
Coto Eliecer,
Nogueiras Luis,
Bobes Julio
Publication year - 2009
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2009.01058.x
Subject(s) - odds ratio , medicine , confidence interval , haplotype , gastroenterology , alcohol dependence , genotype , alcohol , case control study , polymorphism (computer science) , biology , genetics , gene , biochemistry
Background: There is growing evidence for involvement of pro‐inflammatory cytokines in alcohol dependence. The aim of this study was to investigate whether 4 functionally relevant polymorphisms of the interleukin‐1 (IL‐1) and tumor necrosis factor‐alpha genes were associated with alcohol dependence and with measures of clinical severity and treatment outcome. Methods: Two hundred alcohol‐dependent (AD) patients and 420 healthy controls from the same Spanish Caucasian population were genotyped using standard methods. Baseline and 6‐month assessments included alcohol intake, addiction severity, and biomarkers of alcohol intake. Results: Alcohol‐dependent patients showed an excess of IL‐1α−889 C/T [50.8% vs. 39.3%, χ 2 (df) = 7.30 (2), uncorrected p = 0.026, corrected p = 0.104] and IL‐1RA (86 bp) n A1/A1 genotypes [64.8% vs. 50.8%, χ 2 (df) = 12.65 (3), corrected p = 0.020]. The A1/A1 excess was associated with alcohol dependence only in men [69.9% vs. 49.5%, χ 2 (df) = 15.72 (2), corrected p < 0.001]. Six‐month clinical and hematological outcome measures did not vary by genotype of the 4 polymorphisms. Haplotype analysis revealed an excess of the IL‐1α−889 C/IL‐1β +3953 C/IL‐1RA A2 haplotype in the control group compared with AD patients [20.0% vs. 14.1%, χ 2 (df) = 7.25 (1), p = 0.007; odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.46–0.89] and in the abstainers after 6 months of treatment compared with nonabstinent patients [14.7% vs. 6.2%, χ 2 (df) = 5.65 (1), p = 0.017; OR = 2.56, 95% CI = 1.15–5.62]. Conclusions: Our findings provide further tentative evidence of the role of IL‐1 in alcohol dependence as well as evidence that the nature of the associations may be direct, gender‐specific, or involve haplotype effects. However, findings from single association studies constitute tentative knowledge and must be interpreted carefully and precise replication is required.