Using microarray analysis to evaluate genetic polymorphisms involved in the metabolism of environmental chemicals.
The field of molecular biology currently faces the need for a comprehensive method of evaluating individual differences derived from genetic variation in the form of single nucleotide polymorphisms (SNPs). SNPs in human genes are generally considered to be very useful in determining inherited genetic disorders, susceptibility to certain diseases, and cancer predisposition. Quick and accurate discrimination of SNPs is the key characteristic of technology used in DNA diagnostics. For this study, we first developed a DNA microarray and then evaluated its efficacy by determining the detection ability and validity of this method. Using DNA obtained from 380 pregnant Japanese women, we examined 13 polymorphisms of 9 genes, which are associated with the metabolism of environmental chemical compounds found in high frequency among Japanese populations. The ability to detect CYP1A1 I462V, CYP1B1 L432V, GSTP1 I105V and AhR R554K gene polymorphisms was above 98%, and agreement rates when compared with real time PCR analysis methods (kappa values) showed high validity: 0.98 (0.96), 0.97 (0.93), 0.90 (0.81), 0.90 (0.91), respectively. While this DNA microarray analysis should prove important as a method for initial screening, it is still necessary that we find better methods for improving the detection of other gene polymorphisms not part of this study.
Ban
Susumu
S
Department of Public Health, Hokkaido University Graduate School of Medicine, Japan. sban@med.hokudai.ac.jp
Kondo
Tomoko
T
Ishizuka
Mayumi
M
Sasaki
Seiko
S
Konishi
Kanae
K
Washino
Noriaki
N
Fujita
Syoichi
S
Kishi
Reiko
R
D015331:Cohort Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004785:Environmental Pollutants / Q000378:metabolism*; D005260:Female; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011446:Prospective Studies; D015203:Reproducibility of Results
D004785:Environmental Pollutants; D003577:Cytochrome P-450 Enzyme System