Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland.
Brain Res. 2010 Apr 23;1327:103-6. doi: 10.1016/j.brainres.2010.02.072. Epub 2010 Mar 1.
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.
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).
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).
Our results suggest that the MMP-9 gene may play a role in the pathogenesis of alcohol dependence.
基质金属蛋白酶（MMP）是细胞外作用的内肽酶，其底物是细胞外基质和黏附蛋白。在基因多态性研究中，MMP-9 被认为参与了心脏病、癌症、双相情感障碍和精神分裂症的发病机制。在动物模型中，MMP-9 被证明在多种神经元可塑性现象中发挥关键作用，包括学习和记忆以及药物成瘾。
我们研究了 139 个无精神疾病家族，包括 136 名与患者无血缘关系的对照，均为白种人，且性别和民族相匹配。酒精和家族性酒精中毒史通过基于波兰版 SSAGA（酒精中毒遗传学半结构式评估）的结构化访谈进行评估。
我们发现 T 等位基因（已知其产生更高的基因转录活性）从父母到酗酒者的传递具有统计学意义上的优势（59%，p=0.046）。在病例对照研究中，基因型 TT 和 T 等位基因在酗酒者中比在对照组中更为常见（OR=2.6）。
我们的结果表明，MMP-9 基因可能在酒精依赖的发病机制中发挥作用。
