*1.1. Genetic Factors*

Evidence suggests that genetic factors, along with patient susceptibility, may play an important role in the pathogenesis of GOIA [15]. A genetic predisposition can influence a number of factors in the drug interactions, cells, and plaque-induced inflammation. These include the functional heterogeneity of gingival fibroblasts, the collagenolytic activity, the drug-receptor binding, the drug metabolism, collagen synthesis, and many other factors.

Since most types of pharmacological agents that are implicated in GOIA can have negative effects on the flow of calcium ions across cell membranes, it has been postulated that these agents can interfere with the synthesis and function of the collagenase [17]. This mechanism of action has been demonstrated for Cyclosporine. In fact, a recent study in vitro have shown that human gingival fibroblasts that were treated with relevant doses of Cyclosporine show significantly reduced levels of secretion of MMP-1 and MMP-3; these reduced levels can contribute to the accumulation of components of the extracellular matrix [18]. An animal study that showed low mRNA levels of collagenase in situ further supported these results, accompanied by a decrease in phagocytosis and degradation of collagen [19]. The genetic predisposition to GOIA has been studied for cyclosporine, while, for what we know, not ye<sup>t</sup> for amlodipine.
