Interindividual variation

I 97. Efarris, C. C. (1989). Interindividual variation. among humans in carcinogen metabolism, DNA adduct formation and DNA repair. Carcinogenesis 10, 1563-1566. 

Ecogenetics is the study of genetically determined interindividual variation within one species with respect to the response to environmental chemicals or physical environmental factors. 

Within several of the species there is significant interindividual variation (Table 6.2). This is due, in large part, to a lack of control for tooth type. Several recent studies (Bryant et al. 1996 Fricke and O Neil 1996 Stuart-Williams and... 

Shimada, T. et al. (1994). Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals studies with liver micro-somes of 30 Japanese and 30 Caucasians. /. Pharmacol. Exp. Ther., 270,414-23. 

Shu, Y., Cheng, Z. N., Liu, Z. Q. et al. (2001). Interindividual variations in levels and activities of cytochrome P-450 in liver microsomes ofChinese subjects. Acta Pharmacologica Sinica, 22(3),... 

Mutch E, Blain PG, Williams FM. 1992. Interindividual variations in enzymes controlling organophosphate toxicity in man. Hum Exp Toxicol 11 109-116. 

Lown, K. S., Fontana, R. J., Schmiedlin-Ren, P., Turgeon, D. K., Watkins, P. B., Interindividual variation in intestinal MDR1 expression lack of short term diet effects, Gastroenterology 1995, 108, A737. 

Both interindividual variations (responders and non-responders) and variable intraindividual temporal efficacy (short-term responders) for HbF expression may reflect the inherited differences in the metabolic pathways of the drug, in their targets, or in their adaptative mechanisms. These aspects remain to be clarified. 

It was reported that the distribution and activities of esterases that catalyze pyrethroid metabolism using several human and rat tissues, including small intestine, liver, and serum, were examined [30]. The major esterase in human intestine was hCE2. //c/n.v-Permethrin was effectively hydrolyzed by pooled human intestinal microsomes (five individuals), while deltamethrin and bioresmethrin were not. This result correlated well with the substrate specificity of recombinant hCE2. In contrast, pooled rat intestinal microsomes (five animals) hydrolyzed trans-permethrin 4.5 times slower than the human intestinal microsomes. Furthermore, pooled samples of cytosol from human or rat liver were ca. half as hydrolytically active as the corresponding microsome fraction toward pyrethroids however, the cytosolic fractions had significant amounts (ca. 40%) of the total hydrolytic activity. Moreover, a sixfold interindividual variation in hCEl protein expression in human hepatic cytosols was observed. 

Shimada, T., Yamazaki, H., Mimura, M., Inui, Y. and Guengerich, F.P. (1994) Interindividual variations inhuman liver cytochrome P-450 enzymes involved in... 

Gibson, G.G., Plant, N.J., Swales, K.E., Ayrton, A. and El-Sankary, W. (2002) Receptor-dependent transcriptional activation of cytochrome P4503A genes induction mechanisms, species differences and interindividual variation in man. Xenobiotica, 32 (3), 165-206. 

It is important to note that not all of the variability in Lp(a) levels can be explained by isoform size variability in Caucasians, only 40-70% of the variation results from differences in the numbers of kringle IV repeats in the gene (B15, B16). Interindividual variation (—22%) also occurs as a result of as yet undefined cis-acting sequences at the apo(a) locus (B15). In some cases, unrelated individuals with the same-sized apo(a) gene and protein have been shown to possess markedly different plasma Lp(a) concentrations (B15, L5) within families, however, the relationship between apo(a) gene size and plasma Lp(a) con-... 

I.R. Rowland, H. Wiseman, T.A.. Sanders, H. Adelcreutz and E. A. Bowey, Interindividual variation in metabolism of soy isoflavones and lignans influence of habitual diet on equol production by the gut microflora. Nutr. Cancer 36 (2000) 27-32. 

The case of copper is also worthy of special note because several investigations have indicated that while interindividual variations in... 

M. Hosokawa, T. Endo, M. Fujisawa, S. Hara, N. Iwata, Y. Sato, T. Satoh, Interindividual Variation in Carboxylesterase Levels in Human Liver Microsomes , Drug Metab. Dispos. 1995, 23, 1022-1027. 

Many antipsychotics show great interindividual variation in plasma levels and so analysis of therapeutic levels can be important clinically as well as in the research laboratory. In addition, nonresponse to the drugs may actually be due to excessive levels of neuroleptics, a paradoxical situation that requires analysis to identify (Rockland, 1986). Several methods using FID were cited in the previous edition of the Handbook of Neurochemistry but ECD and NPD have both shown utility for the typically low therapeutic levels (Cooper, 1988). GC-FID has been used to analyze levels of clozapine in blood, gastric, and urine samples in fatal cases of overdose with this drug (Ferslew et al., 1998), and olanzapine has been measured in blood and urine samples by GC-NPD in overdoses (Stephens et al., 1998). 4-(4-Chlorophenyl)-4-hydroxypiperidine, a metabolite of haloperidol, was analyzed in urine, plasma, brain, and liver from haloperidol-treated rats by GC-ECD, after derivatization with PFBC under aqueous conditions (Fang et al., 1996). 

In humans, there is considerable interindividual variation in the rate, extent, and pattern of nicotine metabolism in vitro (Messina et al. 1997) and in vivo (Benowitz et al. 1994). Such variation can arise from both genetic and environmental factors. Twin studies allow an estimate of the relative contribution of heritability (i.e., contribution of genes) and environmental influences to a particular phenotype. An investigation in twins of primarily Caucasian ethnicity found that 59% of the variance in nicotine clearance can be attributed to genetic influences (Swan et al. 2005). 

A note should be made on the dominance of a-HBCD in human samples, which is likely to occur because of a diastereomeric shift due to the preferential metabolism of p-HBCD and y-HBCD by cytochrome P450 [34]. Several studies have reported the dominance of a-HBCD in human serum [7]. In contrast, some studies reported y-HBCD to contribute to a higher percentage of the total HBCDs in human tissues [23, 26]. An increase in the percentage of y-HBCD has been reported in highly exposed population and in occupationally exposed workers, with y-HBCD making up to 40% of E-HBCDs [23, 35]. Although the reasons for the different isomer profiles in human tissues from different studies are not yet clear, it is reasonable to hypothesize that they arise from a combination of differences in external exposures (e.g., a-HBCD predominated in both dust and diet of the present study) and interindividual variations in metabolism. 

Interindividual variation in sensitivity is especially obvious with effects of the all-or-none kind. 

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