With the development of pharmacogenetics and pharmacogenomics,pharmacoepigenetics potentially offers another level of explanation for interindividual variations in drug response that cannot be accounted for on the basis of genetic polymorphisms.Many genes encoding enzymes,drug transporters,transcription factors,drug targets,and nuclear receptors are under epigenetic control,which has implications in the context of interindividual variations in drug response as well as drug resistance during cancer treatment.In this overview,we summarize the newest advancement in this field.

BACKGROUND: Peroxisome proliferation-activated receptor-gamma (PPARγ) is the member of nuclear receptor superfamily, and closely related with the formation of atherosclerosis.OBJECTIVE: To investigate the relationship between PPARγ C161→T gene polymorphism and coronary atherosclerotic heart disease (CAHD).DESIGN: Randomized controlled experiment SETTING: Department of Cardiology, Tonai Hospital of Huazhong University of Science and Technology; Department of Cardiology, Zhongnan Hospital of Wuhan University; Center for Human Genome Research,Huazhong University of Science and Technology; Department of Internal Medicine, Affiliated Hospital of Hubei University of Traditional Chinese Medicine; Institute of Geriatrics, Dongzhimen Hospital, Beijing University of Chinese Medicine PARTICIPANTS: Totally 203 CAHD patients aged (65±11) years, including 129 males and 74 females, were the inpatients and outpatients of Zhongnan Hospital of Wuhan University and Tonai Hospital of Huazhong University of Science and Technology from June 2002 to December 2005.And 156 cases of them were diagnosed by coronary arteriongraphy, among which 43 patients without coronary artery affection or with coronary stricture ＜ 50%, and 113 patients with coronary stricture ＞ 50 %. While 89 healthy physical examinees of Han race and mean (59±9) years old were enrolled as control group, including 56 males and 33 females. There was no blood relationship between controls and patients.METHODS: The experiment was conducted at Tongji Hospital of Huazhong University of Science and Technology from June 2002 to December 2005. PPARγ C161→T gene polymorphism was determined by polymerase chain reaction and restriction endonuclease fragment length polymorphisms. The radio-immunity technique, coronary angiography and clinical routine biochemical index were applied to analyze the genotypic frequency and allele frequency distributions as well as the relation between clinical data, biochemical index and different genotypes. The risk factors of CAHD were estimated in the patients of different genotypes.MAIN OUTCOME MEASURES: The genotypic frequency and allele frequency distributions, the relation between clinical data, biochemical index and different genotypes, along with the blood lipid, blood glucose, fasting insulin and body mass index (BMI).RESULTS: Totally 103 CAHD patients and 89 controls were involved in the result analysis of gene polymorphism and yielded different gene distribution frequencies.① In control group, "T" allele frequency was 0.213 and "C" allele frequency was 0.787, and in CAHD group, "T" allele frequency was 0.192 and "C" allele frequency was 0.808. There was no significant difference in the genotypic frequency and C, T allele frequencies between two groups (P ＞ 0.05).② The CC genotype was dominant in CAHD patients with coronary artery lesions, and showed significant differences from "T"allele carriers (CT+TT) (P ＜ 0.05). The CAHD risk in the "T" allele carries (OR: 0.56, 95% CI: 0.24-0.63) was much lower than that in the CC homozygote (OR: 1.92, 95% CI: 1.09-2.54).③ Apolipoprotein B in patients with CC genotype was obviously higher than that in patients with "T" allele (CT+TT) (P ＜ 0.05), and there was insignificant difference in the insulin resistance index (P ＞ 0.05).CONCLUSION: There is an important correlation between the substitution of PPARγ C161→T and CAHD, and "T" allele carriers demonstrate a lower risk of CAHD.