• Title/Summary/Keyword: S-genotype

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Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

  • Lu, Yan-Yan;Huang, Xin-En;Wu, Xue-Yan;Cao, Jie;Liu, Jin;Wang, Lin;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3335-3341
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    • 2014
  • Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

Association of Norepinephrine Transporter Gene and Side Effects of Osmotic-Release Oral System Methylphenidate in Attention-Deficit Hyperactivity Disorder (주의력결핍 과잉행동장애에서 노르에피네프린 수송체 유전자와 오로스 메칠페니데이트 부작용의 연관성)

  • Song, Jungeun;Hong, Hyun Ju;Lee, Byung Ook;Yook, Ki-Hwan
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.25 no.2
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    • pp.82-88
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    • 2014
  • Objectives : The aim of our study was to investigate association of norepinephrine transporter gene (SLC6A2) polymorphism and side effects of osmotic-release oral system methylphenidate (OROS MPH) in children with attention-deficit hyperactivity disorder (ADHD). Methods : We recruited drug naive children with ADHD (N=97). We administered OROS MPH by tolerable dosage. At week 8 of treatment, parents completed the Barkley's side effect rating scale. We analyzed two SLC6A2 single nucleotide polymorphisms (SNPs), rs192303 and rs3785143, with blood of subjects. We compared the frequency and severity of each side effect among SLC6A2 genotypes of 2 SNPs. Results : In the analysis of frequency of each side effect, irritability differed according to rs192303 and rs3785143 genotype. In comparisons of severity, talking less and disinterest differed according to rs192303 genotype. In the case of rs3785143, severities of disinterest and irritability were involved with genotype. Conclusion : Side effects of OROS MPH showed an association with SLC6A2 genotype.

Restorer Genotype for Male Sterile Cytoplasm of Genetic Resources Moderately Resistant to Phytophthora capsici in Capsicum Pepper

  • Kim, Byung-Soo;Ahn, Joon-Hyung;Lee, Jae-Moo;Park, Dong-Guen;Kim, Hye-Yeon
    • Horticultural Science & Technology
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    • v.30 no.1
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    • pp.73-78
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    • 2012
  • KC00256, KC00406, KC00462, KC00463, KC00820, and KC00821, the genetic resources that have previously been reported as moderately resistant to Phytophthora capsici, as well as the line KC01322, a new source of moderate resistance introduced from Laos, were tested against two strains (Pc003 and Pc005) of P. capsici. We also determined the nuclear restorer genotypes of these lines, in regards to their interaction with cytoplasmic male sterility, through crossing the resources with cytoplasmic male sterile Punggok-A (Srfrf) and determining the fertility of the $F_1$ hybrids. The studied lines exhibited a low level of resistance to both the strains of P. capsici compared to highly resistant CM334, but their response was fairly consistent for both P. capsici strains. KC00406, KC00462, KC00463, and KC01322 produced stable, male fertile $F_1$ plants indicating that they are restorers with genotype N(S)RfRf. KC00821 produced male sterile $F_1$ plants and was identified as a maintainer with genotype Nrfrf. The $F_1$ plants of the KC00820 cross, however, set a few male fertile flowers in the greenhouse at seedling stage, then became male sterile after being transplanted to the plastic greenhouse soil in May and remained so to the end of the growing season. Therefore, KC00820 is an unstable maintainer with genotype Nrfrf. The moderate resistance exhibited by these genetic resources may be integrated into breeding programs aimed at promoting higher levels resistance via recurrent selection or hybridization.

Genetic Diversity of Echinococcus granulosus Genotype G1 in Xinjiang, Northwest of China

  • Yan, Bin;Liu, Xiafei;Wu, Junyuan;Zhao, Shanshan;Yuan, Wumei;Wang, Baoju;Wureli, Hazi;Tu, Changchun;Chen, Chuangfu;wang, Yuanzhi
    • Parasites, Hosts and Diseases
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    • v.56 no.4
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    • pp.391-396
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    • 2018
  • Cystic echinococcosis (CE) caused by E. granulosus is a serious helminthic zoonosis in humans, livestock and wildlife. Xinjiang is one of high endemic province for CE in China. A total of 55 sheep and cattle livers containing echinococcal cysts were collected from slaughterhouses in Changji and Yining City, northern region of Xinjiang. PCR was employed for cloning 2 gene fragments, 12S rRNA and CO1 for analysis of phylogenetic diversity of E. granulosus. The results showed that all the samples collected were identified as G1 genotype of E. granulosus. Interestingly, YL5 and CJ75 strains were the older branches compared to those strains from France, Argentina, Australia. CO1 gene fragment showed 20 new genotype haploids and 5 new genotype haplogroups (H1-H5) by the analysis of Network 5.0 software, and the YLY17 strain was identified as the most ancestral haplotype. The major haplotypes, such as CJ75 and YL5 strains, showed identical to the isolates from Middle East. The international and domestic trade of livestock might contribute to the dispersal of different haplotypes for E. granulosus evolution.

Identification of a Novel SNP Associated with Meat Quality in C/EBP${\alpha}$ Gene of Korean Cattle

  • Shin, S.C.;Kang, M.J.;Chung, E.R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.4
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    • pp.466-470
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    • 2007
  • CCAAT/enhancer binding protein ${\alpha}$($C/EBP{\alpha}$) plays an important role in lipid deposition and adipocyte differentiation. In order to find genetic markers to improve the meat quality of Korean cattle, the bovine $C/EBP{\alpha}$ gene was chosen as a candidate gene to investigate its association with carcass and meat quality traits in Korean cattle. A single nucleotide polymorphism (SNP) was identified at position 271 (A/C substitution) of coding region in the $C/EBP{\alpha}$ gene. A PCR-RFLP procedure with restriction enzyme SmaI was developed for determining the marker genotypes. The frequencies of alleles C and A and were 0.374 and 0.626, respectively. The genotype frequencies for CC, AC and AA were 12.9, 49.0 and 38.1%, respectively, in Korean cattle population. The frequencies of genotype were in agreement with Hardy-Weinberg equilibrium. Association analysis indicated that the gene-specific SNP marker of $C/EBP{\alpha}$ showed a significant association with marbling score (p<0.05). The animals with AA genotype had higher marbling score than those with the AC or CC genotype. Although further studies are needed to validate our results, the $C/EBP{\alpha}$ gene could be useful as a genetic marker for carcass and meat quality traits in Korean cattle.

Polymorphysims of CYP17-I Gene in the Exons Were Associated with the Reproductive Endocrine of Japanese Flounder (Paralichthys olivaceus)

  • Ma, R.Q.;He, F.;Wen, H.S.;Li, J.F.;Mu, W.J.;Liu, M.;Zhang, Y.Q.;Hu, J.;Qun, L.
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.6
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    • pp.794-799
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    • 2012
  • The cytochrome P450c17-I (CYP17-I) is one of the enzymes critical to gonadal development and the synthesis of androgens. Two single nucleotide polymorphisms (SNPs) were detected within the coding region of the CYP17-I gene in a population of 75 male Japanese flounder (Paralichthys olivaceus). They were SNP1 (c.C445T) located in exon2 and SNP2 (c.T980C (p.Phe307Leu)) located in exon5. Four physiological indices, which were serum testosterone (T), serum $17{\beta}$-estradiol ($E_2$), Hepatosomatic index (HSI), and Gonadosomatic index (GSI), were studied to examine the effect of the two SNPs on the reproductive endocrines of Japanese flounder. Multiple comparisons revealed that CT genotype of SNP1 had a much lower T level than CC genotype (p<0.05) and the GSI of individuals with CC genotype of SNP2 was higher than those with TT genotype (p<0.05). Four diplotypes were constructed based on the two SNPs and the diplotype D3 had a significantly lower T level and GSI. In conclusion, the two SNPs were significantly associated with reproductive traits of Japanese flounder.

Evaluation of Japanese encephalitis virus vaccine strains currently used in pigs by molecular characterization

  • Lee, Jeong-Ah;Yang, Dong-Kun;Kim, Ha-Hyun;Kim, Sun-Young;Nah, Jin-Ju;Cho, Soo-Dong;Song, Jae-Young
    • Korean Journal of Veterinary Service
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    • v.35 no.3
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    • pp.169-174
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    • 2012
  • Japanese encephalitis virus (JEV) is one of the main causes of viral encephalitis in human and animals. For over 30 years, a live attenuated JEV vaccine strain has been used in the veterinary field, and it is required to conduct quality evaluation studies on the commercial vaccines. For the quality control of live attenuated JEV vaccine, we investigated the nucleotide sequence similarity of prME gene derived from five JEV vaccines commercially available in pigs in Korea. The Vero cells infected with JEV vaccines showed specific cytopathic effect, which was characterized by rounding and detached cells. In the phylogenetic analysis, all of the vaccine strains showed a close relationship with the original vaccine seed strain (Anyang 300) and clustered into the genotype 3. In comparison of the nucleotide and deduced amino acid sequences of prME genes with the original strain, all JEV vaccine strains showed high amino acid similarity ranging from 98.9% to 99.5%, but had several point mutations, probably due to high mutation rates of viral RNA polymerase by several virus passages. Even though the current JEV vaccine strains have been maintained and produced for a long period of time, the genetic characterization of them have been rarely changed. However, since the mid 1990's, molecular epidemiology of JEV has been changed sharply from genotype 3 to genotype 1 in Korea, further studies on new vaccine strains to genotype 1 is required for more effective prevention in the field.

Association of glycophorin A mutant frequency and urinary PAH metabolites influenced by genetic polymorphisms of GSTM1 in incineration workers (소각장 근로자에서 GSTM1의 유전자 다형성이 glycophorin A변이 발현율과 소변내 PAH 대사산물 농도와의 관계에 미치는 영향)

  • 이경호;하미나;최재욱;조수헌;박정규;황응수;강대희
    • Environmental Mutagens and Carcinogens
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    • v.21 no.2
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    • pp.149-155
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    • 2001
  • Eighty-one workers including 38 employees directly incinerating industry wastes were recruited from a company located in South Korea. To evaluate the association between urinary 1-hydroxypyrene glucuronide (1-OHPG) levels, as internal dose of polycyclic aromatic hydrocarbon (PAH) exposure, and glycophorin A (GPA) mutation frequency, as an early biologic effect indicator. Urinary 1-OHPG levels were measured by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11. Erythrocyte GPA variant frequency (NN or NO) was assessed in MN heterozygotes with a flow cytometic assay. The GSTM1 and GSTT1 genotypes were assessed by a multiplex PCR method. The GPA NN phenotype frequency was higher in occupationally exposed group (n=14, mean$\pm$S.D. 6.6$\pm$12.0 in 10/SUP 6/ erythrocyte cells) than in non-exposed group (n=22, 2.1$\pm$3.5). Similarly, the GPA(NO or NN) phenotype frequency was higher in exposed group (n=14, 9.7$\pm$17.3) than non-exposed group (n=22, 4.2$\pm$6.3). The above differences failed to reach statistical significance, but a significant increase was seen in GPA variant frequency levels with increase in urinary 1-OHPG levels (Spearman's correlation: p=0.06 (NO), p=0.07 (NO or NN)). When this association was evaluated by GSTM1 genotype status, the association between GPA mutation and urinary 1-OHPG levels was stronger in individuals with GSTM1 present genotype (Spearmans correlation; r=0.50, p=0.02). These results suggest that the association between urinary 1-OHPG and GPA mutation is be modulated by the GSTM1 genotype.

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Glutathione S-transferase M1 Null Genotype and Hepatocellular Carcinoma Susceptibility in China and India: Evidence from an Updated Meta-analysis

  • Liu, Hong-Zhou;Peng, Jie;Peng, Chun-Yan;Yan, Ming;Zheng, Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4851-4856
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    • 2014
  • Background: Glutathione S-transferase M1 (GSTM1) have been reported to be associated with hepatocellular carcinoma. However, the effect of the GSTMl null genotype was divergent in the literature and we therefore performed the present meta-analysis to explore the relationship in detail. Materials and Metbods: Reported studies were searched from 1990 to March 1, 2014 in PubMed and Wanfang Med Online. The total odds oatio (OR) and 95% CI were calculated and analyzed by Review Manager 5.1 and STATE 12. Results: Total OR was calculated from 26 articles with 3,769 cases and 5,517 controls and the association proved significant (OR [95%CI]=1.50 [1.25, 1.80], P<0.05) in the Chinese population. However, there was no significant association between hepatocellular carcinoma risk among subjects carrying the GSTM1 null genotype (OR [95%CI]=1.20 [0.88-1.64], P=0.24) in subgroups of publication in English and in Indian populations (OR [95%CI]=1.80 [0.80-4.20], P=0.15). Conclusions: The GSTM1 deletion polymorphism might not have a significant effect on the susceptibility of hepatocellular carcinoma overall.

Genetic Polymorphisms of Glutathione S-transferase M1 and Prostate Cancer Risk in Asians: A Meta-analysis of 18 Studies

  • Hu, Zheng-Hui;Lin, Yi-Wei;Xu, Xin;Chen, Hong;Mao, Ye-Qing;Wu, Jian;Zhu, Yi;Xu, Xiang-Lai;Xie, Li-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.393-398
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    • 2013
  • Background: Many studies have investigated associations between the glutathione S-transferase M1 (GSTM1) null polymorphism and risk of prostate cancer, but the impact of GSTM1 in people who live in Asian countries is still unclear owing to inconsistencies across results. Methods: We searched the PubMed, Web of Science, Scopus, Ovid and CNKI databases for studies of associations between the GSTM1 null genotype and risk of prostate cancer in people who live in Asian countries, and estimated summary odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: A total of 18 case-control studies with 2,172 cases and 3,258 controls were included in this meta-analysis, which showed the GSTM1 null genotype to be significantly associated with increased risk of prostate cancer in people who live in Asian countries (random-effects OR=1.74, 95% CI1.44-2.09, P<0.001). Similar results were found in East Asians (OR=1.41; 95% CI: 1.12-1.78; P=0.004) and Caucasians in Asia (OR=2.19; 95% CI: 1.85-2.60; P<0.001). No evidence of publication bias was observed. Conclusions: This meta-analysis of available data suggested that the GSTM1 null genotype does contribute to increased risk of prostate cancer in people who live in Asian countries.