We previously described a polymorphism in exon 4 of the gene encoding the heme biosynthetic pathway enzyme, coproporphyrinogen oxidase (CPOX4), which significantly modifies the effect of mercury exposure on urmary porphyrin excretion in humans. Here, we examined potential consequences of this polymorphism ("CPOX4") on performance within neurobehavioral domains, symptoms, and mood that are known to be affected by elemental mercury (Hg degrees) exposure in human subjects. A behavioral test battery was administered on the day of urine and buccal cell collections for 194 male dentists (DDs) and 233 female dental assistants (DAs) occupationally exposed to Hg degrees for an average of 19 and 10 years, respectively. Subjects had no history of health disorders and were employed for a minimum of 5 years in the dental profession. Respective mean urinary mercury (HgU) levels in DDs and DAs were 3.32 (4.87) mu g/l and 1.98 (2.29) mu g/l. Corresponding indices of chronic occupational Hg degrees exposure, weighted for historical exposure, were 27.1 (20.6) and 15.2 (12.3). The frequencies of the bomogygous common (A/A), heterozygous (A/C), and homozygous polymorpbic (C/C) genotypes were 75%, 23% and 2% for DDs and 73%, 25%, and 2% for DAs, respectively. DDs and DAs were evaluated separately. Regression analyses controlled for age, premorbid intelligence, alcohol consumption, and education. Statistically significant associations with HgU (p < 0.05) were found for nine measures among DDs (BEES Digit Span(forward and backward), and WMS-R Visual Reproduction(N) (Correct), BEES Symbol Digit(Rate), BEES Finger Tapping(Dom/Non-dom) (and Alternate Partialed), Hand Steadiness(Factor1), and BEES Tracking), and eight measures among DAs (BEES Digit Span(forward), BEES Symbol Digit(Rate), BEES Pattern Discrimination (Rate), BEES Trailmaking B, BEES Finger Tapping(Dom/Non-dom, and Alternate) (Partialed), Hand Steadiness(Factor1), and Vibration Sensitivity(Hits)). CPOX4 status was associated with four measures in DDs (BEES Spatial Span(Foward), BEES Pattern Memory(N) (Correct), BEES Symbol Digit(Rate), and BEES Vigilance(Hit)) and five measures in DAs (BEES Digit Span(Forward), WMS-R Visual Reproduction(N) (Correct), BEES Symbol Digit(Rate), BEES Simple and Choice Reaction Time(Move). Both groups experienced an additive effect (no interaction tenn) for HgU and the CPOX4 polymorphisms on the Digit(Rate) whereas DAS also had additive effects for BEES Digit Span(Forward) and for Beck's Depression factor 'Worthlessness'. These exploratory findings suggest that the CPOX4 polymorphism may affect susceptibility for specific neurobebavioral functions associated with mercury exposure in human subjects. (c) 2005 Elsevier Inc. All rights reserved.
