A Gene-Environment Study with the Michigan Dental Association (MDA) Cohort

Faculty Researcher: Niladri Basu, PhD, Assistant Professor of Environmental Health Sciences at the University of Michigan

Research team members at the recruitment booth at the Michigan Dental Association conference.

Research team members at the recruitment booth at the Michigan Dental Association conference.

Mercury is a potent neurotoxic substance of concern to occupationally exposed workers and the general public. While the adverse health effects of mercury are well characterized at high doses little is known about mercury’s effects following chronic exposures to relevant levels. As such, the true health risks and socioeconomic costs of mercury pollution are unclear. Recent studies suggest that several genes mediating the metabolism and neurotoxicity of mercury are polymorphic in humans. We hypothesize that single nucleotide polymorphisms (SNPs) in these genes underlie inter-individual differences in mercury susceptibility. We propose to carry out our studies with the American Dental Association (ADA), an organization with which we have a strong, long-term relationship. In a recent study involving 3,989 paired observations from 2,974 ADA members, we found that changes in peripheral nerve latency are related to low urine mercury concentrations. Here we plan to expand upon these results and carry out a gene-environment study to determine how genetic SNPs (n = 384) relate to inter-individual variations in mercury exposure (inorganic from urine, organic mercury from hair) and peripheral neurological responses in a subset of 500 ADA members. From this pilot project announcement, we are seeking funds to collect additional biological samples through the mail. To our knowledge, this proposed scientific study will be the most comprehensive epidemiological trial to relate mercury exposure and neurological health with genetic polymorphisms. The outcome of this work is expected to significantly enhance our ability to assess the human health risks of mercury to occupationally exposed workers and the general public.

Publications resulting from this project:
Goodrich JM, Wang Y, Gillespie B, Werner R, Franzblau A, Basu N. Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals. Toxicology and Applied Pharmacology. 2011;257(2):301-308. doi:10.1016/j.taap.2011.09.014.

Goodrich JM, Wang Y, Gillespie B, Werner R, Franzblau A, Basu N. Methylmercury and elemental mercury differentially associate with blood pressure among dental professionals. Int J Hyg Environ Health. 2013;216(2):195-201. doi:10.1016/j.ijheh.2012.03.001.

Wang Y, Goodrich JM, Gillespie B, Werner R, Basu N, Franzblau A. An investigation of modifying effects of metallothionein single-nucleotide polymorphisms on the association between mercury exposure and biomarker levels. Environ Health Perspect. 2012;120(4):530-534. doi:10.1289/ehp.1104079.

Wang Y, Goodrich JM, Werner R, Gillespie B, Basu N, Franzblau A. Agreement between clinical screening procedures for neuropathy in the feet. Muscle Nerve. 2012;45(5):653-658. doi:10.1002/mus.23238.

Wang Y, Goodrich JM, Werner R, Gillespie B, Basu N, Franzblau A. An investigation of modifying effects of single nucleotide polymorphisms in metabolism-related genes on the relationship between peripheral nerve function and mercury levels in urine and hair. Sci Total Environ. 2012;417-418:32-38. doi:10.1016/j.scitotenv.2011.12.019.

Grants resulting from this project:
MICHR Pilot Grant. UL1RR024986 (PI:Basu). In vitro- and epidemiology-based gene environment study of mercury with the Michigan Dental Association (MDA) cohort. 04/01/2010 – 07/31/2011.