Susceptibility for ischemic stroke in Korean population is associated with polymorphisms of the Fc gamma receptor IIA.

Fc gamma receptor IIA could influence atherogenic processes through the production of superoxide anions, cytokines, and proteolytic enzymes as well as by oxidation of lipoproteins and enhancement of foam cell formation. In this study, we performed an interaction analysis between FCGR2A polymorphisms and ischemic stroke using direct DNA sequencing after the selection of Fc gamma receptor IIA gene based on genome-wide association study. Four of the FCGR2A polymorphisms, rs7511868 [odds ratio (OR) = 3.21; P = 0.027], rs6427595 (OR = 3.12; P = 0.008), rs7512140 (OR = 5.71; P = 0.002), and rs6696854 (OR = 3.65; P = 0.004) were significantly associated with ischemic stroke. These four polymorphisms still showed significant association after stratification analysis using the Mantel-Haenszel method. In the multivariate logistic regression, the adjusted OR estimates for rs6427595, rs7512140, and rs6696854 were 3.04 (P = 0.016), 4.84 (P = 0.015), and 3.80 (P = 0.006), respectively. The diplotype consisting of two homozygous haplotypes (H2 = AAAC) was significantly associated with ischemic stroke (OR = 17.39; P < 0.001). These results suggest that FCGR2A polymorphisms may be associated with a genetic susceptibility to ischemic stroke in a Korean population.

Recent progress in toxicogenomics research in South Korea.

BACKGROUND: The importance of toxicogenomics was recognized early in Korea and a group of researchers was trying to build up a research infrastructure and educational system. However, since the scale of the Korean pharmaceutical industry, which was expected to play the key role in toxicogenomics was small compared to that of advanced countries, industry-sponsored large-scale research projects and supporting infrastructures have been lacking in Korea. RESULTS: To improve this situation, the Korean government has exerted special efforts to promote toxicogenomics research and development the last few years as an initiative to stimulate a premature drug development industry on par with global competition and launched several large scale research projects recently. Researchers are also trying to keep pace with government efforts by organizing local scientist groups, training young toxicogenomics scientists, and widening the toxicogenomic research efforts to environmental toxicity as well. Research and development from bioinformatics and genomics venture companies are also contributing to uplifting the competitiveness of the toxicogenomics industry. CONCLUSION: Toxicogenomics in Korea is making steady progress in many directions. It is gaining ground by government and related industries as well, the research is diversified to embrace environmental genomics, and local research groups are making strategic links to international research groups such as the MicroArray Quality Control (MAQC) consortium. We expect the advancement of the Korean toxicogenomics research program will be beneficial not only to the local society alone, but also to international scientists as a whole.

An association between RRM1 haplotype and gemcitabine-induced neutropenia in breast cancer patients.

PURPOSE: We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity. PATIENTS AND METHODS: SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers. RESULTS: The incidences of SNPs of breast cancer patients were 1.4% in dCK (626 A>G), 10.8% in DCTD (315 T>C), 40.5% in the first RRM1 (1082 C>A), 44.6% in the second RRM1 (2455 A>G), 44.6% in the third RRM1 (2464 G>A), and 23% in two RRM1 sites (2455 A>G and 2464 G>A) that were similar to those of the normal control group. We found a double SNP of RRM1 (2455 A>G and 2464 G>A) to be the novel haplotype that was associated with a lower frequency of chemotherapy-induced toxicity, such as neutropenia (p < .01) and G-CSF requirement (p < .005). CONCLUSION: RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients.