Urinary Elimination of Coproporphyrins Is Dependent onABCC2Polymorphisms and Represents a Potential Biomarker of MRP2 Activity in Humans

MRP2 encoded byABCC2gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin-Johnson syndrome due to mutation inABCC2gene have elevated urinary coproporphyrin ratio (UCP I/(I + III)). Here we investigated whether this ratio could serve as a biomarker of MRP2 function. Phenotype-genotype relationships were studied in 74 healthy subjects by measuring individual UCP I/(I + III) ratio obtained on 24-hour urine and by analyzing five common SNPs inABCC2gene. The UCP I/(I + III) ratio varied from 14.7% to 46.0% in our population. Subjects with 3972TT genotype had a higher ratio () than those carrying the C allele. This higher UCP I/(I + III) ratio was correlated with a higher level of isomer I excretion. This study provides a proof of concept that UCP I/(I + III) ratio can be used as a biomarker of MRP2 function in clinical studies as it provides quantitative information about thein vivoactivity of MRP2 in a given patient.

Lead exposure in papier mâché workers

Lead exposure was assessed in a random cohort of 70 male papier mâché workers and compared with 35 age and sex matched controls. Blood lead levels in workers were significantly higher than in controls (Mean 68.07 ± 44.64 ug/dl vs 25.52 ± 16.56 ug/dl respectively; P < 0.001). Urinary lead was also higher in workers (128.53 ± 52.61 ug/l) compared to controls (91.18 ± 27.06, P < 0.001), but excretion of urinary coproporphyrin in the two groups was not significantly different (102.78 ± 153.42 vs 70.03 ± 27.06 ug/l, P > 0.05). Blood levels bore a significant correlation with age but did not bear any correlation with the duration of exposure. Various modes of exposure to lead included hand mixing of paints, skin application of the paint to match shades and making point of the brush using lips and the tongue.