• Journal of Genetic Medicine
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• v.5 no.1
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• pp.34-40
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• 2008

Purpose : Preeclampsia is a major cause of maternal and perinatal mortality and morbidity and is considered to be a multifactorial disorder involving a genetic predisposition and environmental factors. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and alterations in the ET-1 system are thought to play a role in triggering the vasoconstriction seen with preeclampsia. The aim of this study was to examine the frequency of the 4 common single-nucleotide polymorphisms (SNPs) (c.1370T>G, c.137_139delinsA, c.3539+2T>C, and c.5665G>T) of the ET-1 gene in normotensive and preeclamptic pregnancies and to investigate whether these SNPs are associated with preeclampsia in pregnant Korean women. Methods : We analyzed blood samples from 206 preeclamptic and 216 normotensive pregnancies using a commercially available SNapShot kit and an ABI Prism 3100 Genetic analyzer. Results : There were no significant differences in genotype or allele frequencies of the 4 SNPs in the ET-1 gene between preeclamptic and normotensive pregnancies. The respective frequencies of the 3 haplotypes (TDTG, GDCT, and TICT; >10% haplotype frequency) were 61%, 13% and 13%, respectively, in preeclampsic pregnancies and 62%, 14% and 12%, respectively, in normotensive pregnancies. The frequencies of these haplotypes were similar for both groups. Using multiple logistic regression analysis, we did not observe an increase in the risk of preeclampsia for the 4 SNPs of the ET-1 gene under either a recessive or dominant model. Conclusion : This study suggests that the 4 SNPs of the ET-1 gene are not associated with an increased risk for preeclampsia in pregnant Korean women.

• Journal of Preventive Medicine and Public Health
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• v.31 no.2 s.61
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• pp.275-284
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• 1998

Activities of enzymes involved in the metabolism of various carcinogenic xenobiotics is one of the most important host factors for cancer occurrence. N-acetyltransferase (NAT) and glutathione S-transferases (GST) are enzymes which .educe the toxicity of activated carcinogenic metabolites. Slow N-acetylation and lack of GST mu (GSTMI) were reported as risk factors of bladder cancer. GST theta (GSTT1), which is another type of GST, was reported to be deleted at higher proportion among Koreans. Since cause of bladder cancer is not fully explained by single risk factor, many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of NAT2, GSTM1 and GSTT1 are risk factors of bladder cancer and to evaluate the effects of their interaction on bladder cancer development. Sixty-seven bladder cancer and 67 age- and sex-matched non-cancer patients hospitalized in Chungbuk National University Hospital from March to December 1996, are the subjects of this case-control study. Questionnaire interview was done and the genotypes of NAT2, GSTM1 and GSTT1 were identified using PCR methods with DNA extracted from venous blood. The effects of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were statistically tested after controlling the other risk factors. The frequencies of slow, intermediate, and rapid acetylators were 3.0%, 38.8%, and 58.2% to. the cases, and 7.6%, 40.9%, and 51.5% for the controls, respectively. The risk of bladder cancer was not associated with the increase of NAT2 activity($\chi^2_{trend}=1.18$, P-value>0.05). GSTM1 was deleted in 68.7% of the cases and 49.3% of the controls ($\chi^2=5.21$, P-value<0.05), and the odds ratio (95% CI) was 2.23 (1.12 - 4.56). GSTT1 deletion, the .ate of which were 26.9% for the bladder cancer patients and 43.3% for the controls, was a significant protective factor against bladder cancer. Smoking history turned out to be insignificant as a risk factor of bladder cancer (OR=1.85, 95% CI: 0.85 - 4.03), and occupation could not be tested because of the extremely small number of occupational history related to the increase of bladder cancer. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion was the only significant risk factor for bladder cancer (OR: 2.56, 95% CI: 1.22-5.36, P-value<0.05), but slow acetylation and GSTT1 deletion were not. These results suggest that GSTM1 deletion may be a significant risk factor of bladder cancer. Since there have been much debates on causal relationship between slow acetylation and GSTT1 deletion, and bladder cancer, further studies are needed.

• Horticultural Science & Technology
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• v.30 no.5
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• pp.557-567
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• 2012

This study was conducted to achieve basal information for the development of tomato cultivars with disease resistances through marker-assisted backcross (MAB). Ten inbred lines with TYLCV, late blight, bacterial wilt, or powdery mildew resistance and four adapted inbred lines with superior horticultural traits were collected, which can be useful as the donor parents and recurrent parents in MAB, respectively. Inbred lines collected were evaluated by molecular markers and bioassay for confirming their disease resistances. To develop DNA markers for selecting recurrent parent genome (background selection) in MAB, a total of 108 simple sequence repeat (SSR) primer sets (nine per chromosome at average) were selected from the tomato reference genetic maps posted on SOL Genomics Network. Genetic similarity and relationships among the inbred lines were assessed using a total of 303 polymorphic SSR markers. Similarity coefficient ranged from 0.33 to 0.80; the highest similarity coefficient (0.80) was found between bacterial wilt-resistant donor lines '10BA333' and '10BA424', and the lowest (0.33) between a late blight resistant-wild species L3708 (S. pimpinelliforium L.) and '10BA424'. UPGMA analysis grouped the inbred lines into three clusters based on the similarity coefficient 0.58. Most of the donor lines of the same resistance were closely related, indicating the possibility that these lines were developed using a common resistance source. Parent combinations (donor parent ${\times}$ recurrent parent) showing appropriate levels of genetic distance and SSR marker polymorphism for MAB were selected based on the dendrogram. These combinations included 'TYR1' ${\times}$ 'RPL1' for TYLCV, '10BA333' or '10BA424' ${\times}$ 'RPL2' for bacterial wilt, and 'KNU12' ${\times}$ 'AV107-4' or 'RPL2' for powdery mildew. For late blight, the wild species resistant line 'L3708' was distantly related to all recurrent parental lines, and a suitable parent combination for MAB was 'L3708' ${\times}$ 'AV107-4', which showed a similarity coefficient of 0.41 and 45 polymorphic SSR markers.

• Journal of Life Science
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• v.22 no.8
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• pp.1057-1063
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• 2012

Epilepsy is the most prevalent chronic neurological disorder and can be controlled by antiepileptic drugs (AEDs) in up to 70% of patients. We performed an association study between adverse drug reactions and the genetic polymorphisms of CYP2C9, CYP2C19, ABCB1, and SCN1A. The clinical data of 83 epilepsy patients who had received AEDs containing carbamazepine (CBZ) were collected. We extracted genomic DNA from peripheral blood and then genotyped CYP2C9 ($CYP2C9^*2$, $CYP2C9^*3$), CYP2C19 ($CYP2C9^*2$, $CYP2C9^*3$), ABCB1 (C3435T), and SCN1A (IVS5N+5 G>A) using direct sequencing. The allele frequencies of $CYP2C9^*3$, $CYP2C9^*2$, $CYP2C9^*3$, ABCB1 (3435C>T), and SCN1A (IVS5N+5 G>A) were 0.93, 0.72, 0.91, 0.61, and 0.55, respectively. Statistically significant differences were indicated from the data obtained. Patients with SCN1A genotype CC or CT were compared with patients with SCN1A genotype TT while using more than 500mg of carbamazepine. We have associated functional polymorphisms with the dose used in regular clinical practice for Korean epilepsy patients who had received antiepileptic drugs (AEDs) containing carbamazepine. For AEDs, we found that one of the SCN1A genotypes is associated with a 500 mg dose. There was no association found with CNS ADR caused by AEDs.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.568-578
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• 2001

Background : Lung cancer is frequently cited as an example of a disease caused solely by exposure to environmental carcinogens. However, there is a growing realization that the genetic constitution is also important in determining individual's susceptibility to lung cancer. This genetic susceptibility may result from functional polymorphims of the genes involved in carcinogen metabolism. In this study, the association between GSTM1 and CYP1A1 polymorphisms and the lung cancer risk in Korean males was investigated. Materials and Method : The study population consisted of 153 male lung cancer patients and 143 healthy male controls. The GSTM1 and CYP1A1 genotypes were determined by multiplex PCR and PCR-RFLP analysis. Result : There were no significant differences in the frequency of the GSTM1 null genotype between the cases and the controls. When the cases were categorized by their histologic type, the frequency of the GSTM1 null genotype in the small cell carcinoma group was higher than those of the controls(67.2% vs 55.9%), but the difference was not statistically significant(OR=1.772 ; 95% CI=0.723-4.340). The distribution of the CYP1A1 MspI genotypes among the cases were similar to those among the controls. When the cases were grouped by their histologic type, the ml/m1, ml/m2, m2/m2 genotypes frequencies among the small cell carcinomas(23.0%, 38.5%, and 38.5%, respectively) were significantly different from those of the controls(36.4%, 46.2%, and 7.4%, respectively, p<0.05). When the m1/m1 genotype was used as a reference, the ml/m2 and m2/m2 genotypes were associated with an increased risk for small cell lung cancer(ml/m2 genotype : OR=1.337, 95% CI=0.453-3.947 ; m2/m2 genotype : OR=3.374, 95% CI=1.092-10.421). Conclusion : These results suggest that the GSTM1 and CYP1A1 genotypes may be a genetic determinant of the risk for lung cancer, particlulary small cell carcinoma. Further investigation is needed to confirm these results.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

• Journal of Animal Science and Technology
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• v.54 no.1
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• pp.1-8
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• 2012

This study aimed to investigate the single nucleotide polymorphisms (SNPs) of the porcine MC4R gene and validate the effect of the MC4R genotype for marker assisted selection (MAS). Six amplicons were produced to analyze the entire base sequences of the porcine MC4R gene and six SNPs were detected (c.-780C>G, c.-135C>T, c.175C>T-Leu59Leu, c.707A>G-Arg236His, c.892A>G-Asp298Asn, and c.*430A>T). Linkage disequilibrium (LD) of the six SNPs was analyzed by performing haploid analysis. There was a perfect linkage disequilibrium in c.-780C>G, c.-135C>T, c.175C>T-Leu59Leu, c.707A>G-Arg236His, and c.*430A>T. Only the c.892A>G (Asp298Asn) SNP showed a very low LD with an $r^2$ value of 0.028 and the D' value of 0.348. As a result, the two SNPs-c.707A>G (Arg236His) and c.892A>G (Asp298Asn)-were selected to extract the genotype frequencies from the 5 pig breeds by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotype analysis method. The SNP frequency of c.707A>G (Arg236His) indicated the presence of the A (His) allele only in Yorkshire, while the G allele was fixed in the KNP, Landrace, Berkshire, and Duroc. Association analysis was carried out in 484 pigs with the c.707A>G (Arg236His) SNP and the meat quality traits of four different pig cross populations: a significant association was noted in crude fat, sirloin moisture, meat color, and the degree of red and yellow coloration. The frequency of the c.892A>G(Asp298Asn) SNP genotype varied among the breeds; while Duroc showed the highest frequency of the A (Asn) allele, KNP showed the highest frequency of the G (Asp) allele. Association analysis was carried out in 1126 pigs with the c.892A>G (Asp298Asn) SNP and the meat quality traits of four pig populations: a highly significant linkage was noted in the back-fat thickness (P<0.002). It was found that the back-fat thickness was higher in individuals with the AA genotype than in those with the AG or GG genotype. Thus, in this study, we verified that the c.892A>G (Asp298Asn) SNP in the pig MC4R gene has a sufficient effect as a gene marker for MAS in Korean pork industry.