Polymorphisms of the IL-1 gene complex are associated with alcohol dependence in Spanish Caucasians: data from an association study.
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-1alpha-889 C/T [50.8% vs. 39.3%, chi(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%, chi(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%, chi(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-1alpha-889 C/IL-1beta +3953 C/IL-1RA A2 haplotype in the control group compared with AD patients [20.0% vs. 14.1%, chi(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%, chi(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.
Saiz
Pilar A
PA
Department of Psychiatry, School of Medicine, Centro de Investigación Biomédica en Red de Salud Mental, University of Oviedo, Julián Claveria 6-3, Oviedo, Spain. frank@uniovi.es
Garcia-Portilla
Maria P
MP
Florez
Gerardo
G
Corcoran
Paul
P
Arango
Celso
C
Morales
Blanca
B
Leza
Juan C
JC
Alvarez
Sandra
S
Díaz
Eva M
EM
Alvarez
Victoria
V
Coto
Eliecer
E
Nogueiras
Luis
L
Bobes
Julio
J
D000328:Adult; D000437:Alcoholism / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D000483:Alleles; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D044465:White People
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D004247:DNA