DNA Repair and Detoxifying Gene Polymorphisms in Patients with Multiple Sclerosis and Dental Amalgam Fillings

Objective: The present study was designed to evaluate the influence of Metallothionein ( MT ), detoxifying ( GSTs ) and repair ( OGG1, XRCC1 ) gene polymorphisms on the risk of Multiple Sclerosis (MS) related to metal exposure. Materials and Methods: One heavy (Mercury; Hg) and two essential metals (Copper; Cu and Zinc; Zn) from dental amalgam fillings were selected. Our study subjects were divided into 4 groups, namely, MS patients not carrying dental amalgam fillings (n=20); patients carrying dental amalgam fillings (n=20); control subjects not carrying dental amalgam fillings (n=20) and control subjects carrying dental amalgam fillings (n=20). The levels of urinary metals detected with Atomic Absorption Spectrometry (AAS) and gene polymorphisms were analyzed with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR- RFLP). Results: Subjects with polymorphic OGG1 genotype had 3 times higher MS risk and subjects with dental amalgam fillings had significantly more urinary Hg levels compared to subjects without dental amalgam fillings. Conclusion: Considering the information on urinary metal levels, OGG1 Ser326Cys gene polymorphisms may modify the repairing of oxidative products. However, no significant association between OGG1 gene polymorphism and urinary Hg levels was observed. Many studies have proposed the association of MS with toxic metals (aluminum; Al, lead; Pb and mercury; Hg) and essential metals (Zinc; Zn, Cu) (2; 3). At present, 2.3 million people in the world suffer from MS; thus, researchers investigate the factors which have roles in MS pathogenesis. Recently, considerable attention has been paid to the risk of dental amalgam fillings on the development of MS due to their potential neurotoxic effects. The presence of dental amalgam fillings is suggested to be associated with a variety of neurological disorders. Therefore, studies on associations with neurological diseases and metal exposures take into account dental amalgam fillings for accurate evaluation. Mercury is a naturally occurring element released from a variety of sources such as natural sources and the burning of fossil fuels. 3-4 % of total Hg sources are dental amalgam fillings consisting of 50 % metallic Hg mixed with an alloy (silver, tin and Cu) (4). Animal studies showed that Hg released from dental amalgam fillings is absorbed and accumulated in various organs such as kidney, brain, liver and lungs (5). There are comparative studies on MS patients with or without dental amalgam fillings. Significant correlations were shown between urinary Hg levels and the number of amalgam fillings. Removal of amalgam fillings results in a significant reduction in body burden of Hg (6). There have been controversial studies on removing amalgam fillings or chelation therapy on MS patients. Chelation therapy relieves general symptoms due to decrease burden of metals. When amalgam fillings are removed, small amounts of Hg are slowly released and accumulate in various tissues especially in brain tissue (7). The first report between amalgam fillings and MS reported a strong correlation. Certain health may occur amalgam fillings We found statistically significant higher MS risk in subjects with OGG1 Cys/Cys genotypes than subjects with OGG1 Ser/Ser genotypes. However, we did not find any impact of XRCC1 Arg399Gln gene polymorphism and of the levels of Hg, Zn and Cu in the risk of MS. Quite recently, considerable attention has been paid to dental amalgam fillings and their potential neurological toxic effects in terms of their metal content especially, Hg. As reported by “Food and Drug Administration (FDA) White Paper” (42) the weight of evidence from human clinical and epidemiological studies did not support the hypothesis that Hg exposure from amalgam fillings causes adverse health effects. According to FDA (42), the range of urinary Hg levels in subjects without any occupational exposure is up to 20 µg L -1 . Urinary Hg levels were known to increase by 6 % for each amalgam surface, but they were not associated with fish consumption. For this reason, except for occupational exposure, it was suggested that amalgam fillings constitute the main source of Hg exposure (31).