Functional polymorphism of matrix metalloproteinase-9 (MMP-9) gene in alcohol dependence: family and case control study.

AIM: Matrix metalloproteinases (MMP) are extracellularly acting endopeptidases, whose substrates are extracellular matrix and adhesion proteins. In the gene polymorphism studies MMP-9 has been suggested to be involved in the pathogenesis of heart disease, cancer, bipolar disorder, and schizophrenia. In animal models MMP-9 has been shown to play a key role in a variety of neuronal plasticity phenomena, including learning and memory as well as drug addiction.

METHOD: We studied 139 families, Caucasians, with no history of psychiatric disorder of ICD-10 other than alcohol or nicotine dependence. The control subjects were 136 unrelated individuals, matched for ethnicity and gender, with no mental disorder. Alcohol and family history of alcoholism were assessed by means of a structured interview, based on the Polish version of SSAGA (Semi-Structured Assessment on Genetics in Alcoholism).

RESULTS

We found a statistically significant preferential transmission of the T allele (known to produce higher gene transcriptional activity) from parents to alcoholics (59%, p=0.046). In a case-control study genotype TT and T alleles were significantly more frequent in the alcoholics than in the controls (OR=2.6).

CONCLUSION

Our results suggest that the MMP-9 gene may play a role in the pathogenesis of alcohol dependence.