[Detecting genetic polymorphisms of CYP1 A1 and GSTM1 simultaneously with oligonucleotide microarray].
Cytochrome P4501A1 plays a major role in the bioactivation of a number of tobacco procarcinogens. Glutathione S-transferase( GSTM1), a member of the class of GST gene family, has been shown to be polymorphic because of gene deletion resulting in a failure to express the GSTM1 gene in 50% approximately 60% of individuals. Some CYP1 A1/GSTM1 null genotype combinations seem to predispose the lung, esophagus, and oral cavity of smokers to an even higher risk for cancer or DNA damage, requiring, however, confirmation. An easy and reliable oligonuleotide microarray approach validated through direct sequencing method is developed in order to accurately detect single nucleotide polymorphisms of CYP1 A1 gene and discriminate the presence and absence of GSTM1 gene. The m1 (Msp I) and m2 (Ile462Val) polymorphisms of CYP1 A1 gene and GSTM1 null genotype were also determined in a random population of 84 healthy, unrelated volunteers with developed microarray-based method. Of 84 cases, 47.6% were calssified as GSTM1 null, close to the published data. It's interesting that there lack three genotypes of m1 -m2 locus in the population: TT-AG, TT-GG and TC-GG. However, according to the data of the genotype frequencies independently happened at both m1 and m2 site, the combination frequencies of above three genotypes are 11.4%, 2.6%, and 3.1% respectively. Therefore we assume that the haplotypes of m1 -m2 are only T-A, C-A and C-G, but not T-G, as it were,there is no recombination happened between m1 site and m2 site. The frequencies of three haplotypes of T-A, C-A and C-G, calculated through corresponding genotypes, are 69.6%, 7.7% and 22.6% respectively.
Liu
San-Zhen
SZ
State Key Laboratory of Genetic Engineering, Institute of Genetics, College of Life Science, Fudan University, Shanghai 200043, China.
Li
Yao
Y
Li
Rong-Yu
RY
Qiu
Min-Yan
MY
Shen
Wei-Wen
WW
Gu
Jia-Yuan
JY
Wang
Yu
Y
Sun
Mei-Qian
MQ
Mao
Yu-Min
YM
Xie
Yi
Y
D001483:Base Sequence; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase