A variety of studies in animals (Aten, et al., 1992; Druet, et al., 1978; Hirszel, et al.,1985; Hultman and Enestrom, 1992; Matsuo, et al., 1987; Michaelson, et al., 1985; Pelletier,et al., 1990; Pusey, et al., 1990; Roman-Franco, et al., 1978; van der Meide, et al., 1993) (seereviews by Silbergeld, et al., 2005; Nielson & Hultman, 2002; ATSDR, 1999) demonstrate the occurrence of autoimmune glomerulonephritis upon exposure to Hg° in genetically susceptible animals.
Autoimmune glomerulonephritis results in observed proteinuria as a result ofautoantibodies reacting with renal tissues. Some human evidence supports the existence of animmunologically mediated renal impact of Hg°, with deposition of IgG, immune complexes and/or complement C3 along the glomerular basement membrane (Lindqvist, et al., 1974; Tubbs, et al., 1982). This has been interpreted as evidence of a potential genetic predisposition toimmunologically mediated renal response to Hg exposure, although the existence of a genetic polymorphism coding for the requisite genetic susceptibility has not been reported.
Echeverria, et al., (Echeverria, et al., 2006, 2005; Woods, et al., 2005; Heyer, et al.,2004) have recently identified polymorphisms in genes encoding for brain-derived neurotrophicfactor (BDNF). Various detriments in neurobehavioural performance (Echeverria, et al., 2006,2005) and in symptoms and mood (Heyer, et al., 2004) were associated with the presence ofthe BDNF polymorphism (frequency = _25–35% among study subjects (193 male dentists;233 female dental assistants)), independent of Hg exposure level. The combined effects of thepolymorphism and Hg exposure appeared to be additive. These results suggest that the presence of the polymorphism does not necessarily put persons at risk of an enhanced toxic response to Hg exposure. Rather, persons with the polymorphisms might respond to Hg exposures similarly to those without, but from a diminished starting point with respect to neurobehavioural performance.
The presence of a polymorphism for coproporphyrinogen oxidase (CPOX4; frequency =15% of subjects in Woods, et al. (2005); and 25% of study subjects in Echeverria, et al. (2006))has also been observed and is associated with detriments in neurobehavioural responseindependent of Hg exposure. As with BDNF, the influence of the CPOX4 polymorphism and Hgexposure appeared to be additive.
