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Abstract
Previous studies reported that polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) induced hepatic cytochrome P-4501A1 (CYP1A1). The aim of this study was to examine the interactive influence of CYP1A1 genotypes and PCDD/Fs exposure on liver function profile. PCDD/Fs levels and liver function parameters were determined in serum and correlated with genetic polymorphism of CYP1A1/Msp 1 in 225 human volunteers who had no or minimal occupational exposure to PCDD/F. The results showed that the highest glutamate pyruvate transaminase (GPT) activity levels were found in subjects with homozygous variant CYP1A1/Msp 1, followed by heterozygous variant, and finally homozygous wild type for those individuals whose serum PCDD/Fs levels were higher than 17.4 pg WHO-TEQ/g lipid. Data suggest that GPT activity levels may be modified by interaction of CYP1A1/Msp 1 genotype with dioxin after adjustment for age, alcohol consumption, and history of liver illness. Further studies are needed to characterize the variation in other related genes to verify whether a correlation exists between serum PCDD/Fs levels and adverse health effects.
We extend our heartfelt appreciations to the participants, the local Environmental Protection Bureau for sampling assistance, and our colleagues at the Research Center of Environmental Toxic Trace Substances, National Cheng Kung University Medical College, for sampling and analytical support. This work was supported in part by grants from the Environmental Protection Administration, Government of Republic of China.
Notes
a Number (%)
b Mean ± standard deviation (minimum–maximum).
c pg WHO-TEQ/g lipid.
a Significant difference from wild type (p < .05).
a The study subjects were grouped according to quartiles of their serum PCDD/Fs levels.
b Significant at p < .05 by Student’ t-test.
a The study subjects were grouped according to median of their serum PCDD/Fs levels.
b Significant difference at p < .05 by Student's t-test between groups with low to high serum PCDD/Fs levels.
a Significant at p < .05.
Group 1: Subjects with low serum PCDD/Fs level and both alleles are wild type or heterozygous type, n=92.Group 2: Subjects with high serum PCDD/Fs level and both alleles are wild type or heterozygous type, n=93. Group 3: Subjects with low serum PCDD/Fs level and both alleles are variant type, n=18. Group 4: Subjects with high serum PCDD/Fs level and both alleles are variant type, n=18.