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김정현,정현섭,김령효,신희정,나한성,정면우,신형두 한국유전학회 2015 Genes & Genomics Vol.37 No.3
Low density lipoprotein receptor (LDLR) playsan important role in plasma lipoprotein metabolism andpharmacological responses. Although mutations of LDLRand their functional associations with plasma LDL cholesterolconcentrations have been described, no comprehensivecomparisons of LDLR variants among populationsare established. The aim of this study is to define the distributionof single nucleotide polymorphisms (SNPs) ofLDLR and to discover novel variants across populationgroups. A total of 288 DNAs from 96 Korean, 48 Chinese,48 Japanese, 48 African-American, and 48 European-American subjects were resequenced. A total of 59 SNPs(18 in the coding regions, 37 in the introns, and 4 in the 30-untranslated region) were identified, including eight novelvariants. Polymorphisms of LDLR showed significantlydifferent distributions in comparisons among ethnicpopulation groups (P\0.05, Fisher’s exact test). Moreover,almost all of these differently distributed SNPs werecommon variants. Notably, prevalent variations—rs1003723, rs1799898, rs688, rs5925, rs6413504 in Europeans,nonsynonymous rs11669576 (Ala391Thr) in Africans,and rs14158 in Asians—were observed. In further insilico analyses for the novel SNPs, 2 intronic variants(?17716G[A in the intron 5 and ?38569A[C in theintron 16) were predicted as potential branch point sites foralternative splicing. Although this study is not free fromlimitations such as insufficient sample size and no functionalstudies on the novel SNPs, our findings providessupporting information about LDLR genetic variabilityamong ethnic groups and pharmacogenetics studies forplasma lipoprotein metabolism.
김정현,신형두,정현섭,박병래,김영효,신희정,나한성,장명우 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.1
Recently, CYP2A6, CYP2B6, CYP2C8, andCYP2E1 have been reported to play a role in the metaboliceffect of pharmacological and carcinogenic compounds. Moreover, genetic variations of drug metabolism geneshave been implicated in the interindividual variation indrug disposition and pharmacological response. To definethe distribution of single nucleotide polymorphisms (SNPs)in these four CYP2 family genes and to discover novelSNPs across ethnic groups, 288 DNAs composed of 48African-Americans, 48 European-Americans, 48 Japanese,48 Han Chinese, and 96 Koreans were resequenced. A totalof 143 SNPs, 26 in CYP2A6, 45 in CYP2B6, 29 in CYP2C8,and 43 in CYP2E1, were identified, including 13 novel variants. Notably, two SNPs in the regulatory regions, apromoter SNP rs2054675 and a nonsynonymous rs3745274(p.172Q[H) in CYP2B6, showed significantly differentminor allele frequencies (MAFs) among ethnic groups(minimum P = 4.30 9 10-12). In addition, rs2031920 inthe promoter region of CYP2E1 showed a wide range ofMAF between different ethnic groups, and even amongother various ethnic groups based on public reports. Among 13 newly discovered SNPs in this study, 5 SNPswere estimated to have potential functions in further insilico analyses. Some differences in genetic variations andhaplotypes of CYP2A6, CYP2B6, CYP2C8, and CYP2E1were observed among populations. Our findings could beuseful in further researches, such as genetic associationswith drug responses.
Expression of CYP2A6, CYP2D6 and CYP4A11 Polymorphisms in COS7 Mammalian Cell Line
이혜자,박미경,박영란,김동학,윤철호,천영진,신희정,나한성,정면우,이창훈 한국독성학회 2011 Toxicological Research Vol.27 No.1
The cytochrome P450 (P450, CYP) are the superfamily of heme-containing monooxygenase enzymes, found throughout all nature including mammals, plants, and microorganisms. Mammalian P450 enzymes are involved in oxidative metabolism of a wide range of endo- and exogenous chemicals. Especially P450s involved in drug metabolisms are important for drug efficacy and polymorphisms of P450s in individuals reflect differences of drug responses between people. To study the functional differences of CYP2A6, CYP2D6, and CYP4A11 variants, we cloned the four CYP2A6, three CYP2D6, and three CYP4A11 variants, which were found in Korean populations, in mammalian expression vector pcDNA by PCR and examined their expressions in COS-7 mammalian cells using immunoblots using P450 specific polyclonal antibodies. Three of four CYP2A6, two of three CYP4A11, and two of three CYP2D6 variants showed expressions in COS-7 cells but the relative levels of expressions are remarkably different in those of each variants. Our findings may help to study and explain the differences between functions of CYP variants and drug responses in Korean populations.
Teratogenic Effects of Nano- and Micro-sized Particles of Zinc Oxide during Mouse Organogenesis
윤정민,정아영,Chun-Mei Lin,이종걸,정기연,나한성,정면우,이범준,윤영원,남상윤 충북대학교 동물의학연구소 2011 Journal of Biomedical and Translational Research Vol.12 No.2
Zinc oxide nanoparticles (nZnO) are used in a various range including ceramic manufacture, photocatalysis, UV filters, and food industry. However, very little is known about effects of micro- and nano-particle during mouse embryo organogenesis. To determine whether ZnO affects size-dependent anomalies during embryonic organogenesis, mouse embryos were cultured for 2 days with 300 ug/ml micro ZnO (mZnO; 80 ± 25 μm) and nZnO (< 100 nm) and then the developmental changes were investigated, quantity of Zn by inductively coupled plasma mass spectrometry analysis, and expression patterns of various antioxidant enzymes in the embryos were investigated. Embryos exposed to mZnO or nZnO exhibited severe growth and development retardation. In the embryos exposed to mZnO and nZnO, yolk sac diameter, crown-rump length, and head length were significantly diminished. The morphological parameters including yolk sac circulation, allantois, flexion, heart, hindbrain, midbrain, forebrain, otic system, optic system, branchial bars, maxillary process, mandibular process, olfactory system, caudal neural tube, forelimb, hindlimb, and somites in mZnO and nZnO-treated groups were significantly decreased. Zn absorption of nZnO-treated group was significantly higher than that of mZnO-treated group. CuZn-SOD, Mn-SOD, cGPx and PHGPx mRNA levels were significantly decreased in ZnO-treated group. In addition, antioxidant enzymes mRNA expressions of nZnO group were siginificantly diminished less than those of the mZnO treated group. These findings indicate that 300 ug/ml ZnO showed abnormality and nZnO may have more severe effect than mZnO in developing embryos.