The Importance Of Determining Pon1 Status

In recent years, the importance of determining an individuals' PON1 status has been repeatedly highlight-ed.[7,9-13] The term PON1 status includes both the PON1192 genotype as well as PON1 activity. The concept was prompted by examination of a number of epidemi-ological studies, which examined only the PON1192 and PON155 genotypes, without considering the large

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Fig. 1 The PON1 gene is located on human chromosome 7, near the genes encoding PON2 and PON3. The expanded PON1 gene diagram shown illustrates the locations and frequencies of single nucleotide polymorphisms (SNPs) that have been identified in the PON1 gene, with SNP locations indicated by vertical lines below the gene structure diagram. The numbered boxes correspond to the nine exons found in PON1. The length of each line indicates the frequency of that SNP in the population. In addition to the previously identified SNPs that result in amino acid substitutions at L55M and Q192R, 166 new SNPs were identified by the UW/FHCRC Variation Discovery Resource (Seattle SNPs). The PON1 SNP diagram at the bottom was created at the SeattleSNPs web site (http:// pga.gs.washington.edu/), using the GeneSNPs public web resource (http://www.genome.utah.edu/genesnps) available from the Utah Genome Center. (View this art in color at www.dekker.com.)

Fig. 1 The PON1 gene is located on human chromosome 7, near the genes encoding PON2 and PON3. The expanded PON1 gene diagram shown illustrates the locations and frequencies of single nucleotide polymorphisms (SNPs) that have been identified in the PON1 gene, with SNP locations indicated by vertical lines below the gene structure diagram. The numbered boxes correspond to the nine exons found in PON1. The length of each line indicates the frequency of that SNP in the population. In addition to the previously identified SNPs that result in amino acid substitutions at L55M and Q192R, 166 new SNPs were identified by the UW/FHCRC Variation Discovery Resource (Seattle SNPs). The PON1 SNP diagram at the bottom was created at the SeattleSNPs web site (http:// pga.gs.washington.edu/), using the GeneSNPs public web resource (http://www.genome.utah.edu/genesnps) available from the Utah Genome Center. (View this art in color at www.dekker.com.)

variability of PON1 protein levels within each genotype (Fig. 2). Indeed, PON1 levels are at least as important as genotype in determining rates of clearance of oxidized lipids, as well as determining resistance to organophos-phate toxicity.[10] By plotting the rates of diazoxon hydrolysis against paraoxon hydrolysis at high salt concentration (2 M NaCl) for individuals in a population, the subjects are clearly divided into three groups: individuals homozygous for PON1Q192, heterozygotes (PON1Q/R192), and individuals homozygous for PON1r192; in addition, information of PON1 activity levels is also obtained (Fig. 2; Ref. [9]). The procedure can be easily carried out in 96-well microtiter plate readers capable of following continuous enzyme kinetics at the appropriate wavelength (for details, see Ref. [14]). For this assay, plasma from blood collected in heparin or citrate can be used, but not ethylenediaminetetraacetic acid (EDTA) plasma, because EDTA irreversibly inhibits PON1. The accuracy of this PON1 status approach to determine the PON1192 functional genotype has been verified by direct genotyping using a polymerase chain reaction (PCR) method,[2,14] and has been found to be close to 100%. Individuals with discrepant assignments have been found to have one dysfunctional PON1 allele.[15] For example, several individuals were geno-typed as 192 Q/R heterozygotes by PCR, but the functional enzyme analytic assay followed by the sequencing of their PON1 genes demonstrated that one or the other PON1 alleles were defective.[15] Methods for genotyping other polymorphisms in the 5' promoter region (e.g., — 108TC), as well as newly discovered polymorphisms in the coding region (e.g., W194X), have also been described.[14]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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