• Journal of Gastric Cancer
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• v.22 no.4
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• pp.348-368
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• 2022

Purpose: Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features. Materials and Methods: The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay. Results: The PLK2 C_rs15009-C_rs963615 haplotype was under-represented in the GC group compared to that in the control group (P_corr=0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM T_rs228589-A_rs189037-G_rs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC. Conclusions: PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2407-2410
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• 2016

Background: Response to antiviral therapy has been linked to different genotypes and this impacts on clinical management. Data on general responses to standard interferon (IFN) against HCV infection exists but little is known regarding HCV genotype specific responses. Purpose: Therefore, we attempted to determine genotype specific responses of chronic HCV patients, having different HCV genotypes, to standard IFN and ribavirin combination therapy administered for a period of six months in Kybher Pakhtunkhwa province of Pakistan. Materials and Methods: HCV genotype was determined for all serum samples. Each patient received standard IFN combination therapy with ribavirin administered at dose of 3 MIU three times a week and 800-1200 mg/day, respectively, for a period of six months. After completion of this therapy, PCR was performed for all course completed subjects. Results: Out of total 51 selected patients the most abundant genotypes were 3a (49.0%) and 1a (21.6%) followed by 3b (9.8%), 1b (7.84%), 2a (7.84%) and untypable (3.94%). Moast responsive genotypes were 2a followed by 3a, with end of treatment responses of 77.7%, and 72.2%. Responses for 3b, 1b and untypable were 66.7%, 33.3% and 0%, respectively. Conclusions: IFN response is efficient in case of 2a and 3a genotypes while in case of untypable genotypes, further categorization is required to know about genomic sequences and to adopt some new regimes against these genotypes.

• Journal of Life Science
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• v.16 no.2 s.75
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• pp.345-351
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• 2006

Streptococcus sp. were isolated from cultured flounder (Paralichthys olivaceus) having Streptococcosis during 2004 to 2005 in Jeju Island. Ninety four Streptococcus iniae strains were isolated using biochemical test and multiplex PCR assay. Three genotypes (A, B, C-type) of S. iniae were appeared in the RAPD analysis and they showed international or local genetic polymorphism. Presently, S. iniae having A-type is a dominant S. iniae genotype in Jeju and showed band patterns at about 550, 850, 1000, 1300 and 2000 base pares. In this study, the reported P14 random primer, that used to distinguish serotypes of S. iniae could not be applied to distinguish Jeju island S. iniae's genetic polymorphism.

• Journal of Gastric Cancer
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• v.7 no.1
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• pp.9-15
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• 2007

Purpose: DNA methylation is an important epigenetic factor in tumorigenesis. We hypothesized that polymorphism of the promoter of the DNA methyltransferase 3b (DNMT3b) genes, which are responsible for regulating the methylation status of tumor suppressor genes, are associated with increased risk of gastric cancer. Materials and Methods: In this hospital-based case-control study, to determine the role of this polymorphism of the promoter of DNA methyltransferase 3b (DNMT3b) genes in gastric cancer, we genotyped 176 cases and 70 control subjects. To determine the genotype, we used a polymerase chain reaction restriction fragment length polymorphism assay. We compared alleles and genotypes between the two groups and revealed an association of DNMT3b promoter polymorphism with increased risk of gastric cancer in the Korean population. Results: Genotype frequencies were 14.8% (Cytosine-Cytosine), 71.6% (Cytosine-Thymine), and 13.6% (Thymine- Thymine) in the case patients and 40.0% (Cytosine-Cytosine), 42.9% (Cytosine-Thymine), and 17.1% (Thymine-Thymine) in the control subjects, respectively. Compared with CC homozygotes, CT heterozygotes had a 4.523-fold increased risk (OR, 2.13; 95% CI, 2.324~8.803), and the TT homozygotes had a 2.154-fold elevated risk (OR, 1.42; 95% CI, 0.899~85.165). For the T variant genotype (CT+TT), there was a 3.846-fold increased risk (OR, 1.88; 95% CI, 2.040~7.251). However, no significance was observed in the genotype distributions of both polymorphisms according to histopathology, stage of stomach cancer. The Ssame results were observed with Helicobacter infection. Conclusion: DNMT3b promoter polymorphism, especially the T variant genotype, is associated significantly with thean increased risk of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8837-8842
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• 2014

Background: Hepatitis C virus (HCV) infection is an important cause of liver cancer in Thailand. The highest prevalence of anti-HCV positive among Thai blood donors is found in the northeastern region. The present analysis of the genotype distribution among anti-HCV positive northeastern-Thai blood donors was conducted to provide a base for the epidemiological pattern of HCV infection in this region. Materials and Methods: A total of 112 HCV seropositive healthy blood donors were randomly selected and tested for the presence of HCV-RNA by RT-PCR. HCV-RNA positive samples were genotyped by direct sequencing at core region genomes and confirmed by phylogenetic analysis. Results: HCV viremia was found in 94.6% (106/112) of HCV seropositive blood donors. There were 3 major genotypes distributed among this population. HCV genotype 3a was the most prevalent (71.7%) followed by genotypes 1a (7.5%), 1b (7.5%), 6i (3.8%), 6f (2.8%) and 6n (1.9%). Conclusions: HCV genotype 3a in asymptomatic infections in northeastern Thailand is significantly higher than other previous reports. Subgenotype 6 prevalence is less than in neighboring countries and distribution patterns differ. The findings are relevant as predictors for using interferon therapy in this population.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.9
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• pp.1228-1235
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• 2014

The swine leukocyte antigen (SLA)-DRA locus is noteworthy among other SLA class II loci for its limited variation and has not been investigated in depth. This study was investigated to detect polymorphisms of four exons of SLA-DRA gene and its association with piglet diarrhea in Landrace, Large White and Duroc pigs. No polymorphisms were detected in exon 3, while 2 SNPs (c.178G>A and c.211T>C), 2 SNPs (c.3093A>C and c.3104C>T) and 5 SNPs (c.4167A>G, c.4184A>G, c.4194A>G, c.4246A>G and c.4293G>A) were detected in exon 1, exon 2 and exon 4 respectively, and 1 SNP (c.4081T>C) in intron 3. Statistical results showed that genotype had significant effect on piglet diarrhea, individuals with genotype BC had a higher diarrhea score when compared with the genotypes AA, AB, AC and CC. Futhermore, genotype AC had a higher diarrhea score than the genotype CC in exon 1 (p<0.05); diarrhea scores of genotype AA and BB were higher than those of genotypes AC and CC in exon 2 (p<0.05); individuals with genotype AA had a higher diarrhea score than individuals with genotype AB and BB in exon 4 (p<0.05). Fourteen common haplotypes were founded by haplotype constructing of all SNPs in the three exons, its association with piglet diarrhea appeared that Hap2, 5, 8, 10, and 14 may be the susceptible haplotypes and Hap9 may be the resistant haplotype to piglet diarrhea. The genetic variations identified of the SLA-DRA gene may potentially be functional mutations related to piglet diarrhea.

• Journal of Nutrition and Health
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• v.38 no.3
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• pp.211-218
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• 2005

Elevated homocysteine concentration is known to be related to placental abruption, spontaneous abortion, and many adverse pregnancy outcomes. The purpose of this study was to investigate the effects of folic acid supplementation ($1000{\cal}ug$ per day) and 5, 10 methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype on serum homocysteine and B vitamin levels in 50 infertile women ($31.2{\pm}3.2\;years$). Blood sampling was performed at baseline and at the end of folic acid supplementation period. In infertile women, serum folate and vitamin $B_{12}$ concentrations were significantly higher in post-supplementation than those in pre-supplementation. Serum homocysteine concentration was significantly lower in post-supplementation than that in pre-supplementation. However, serum homocysteine levels were still higher in the T/T genotype than those in the C/C or C/T even after folic acid supplementation. Serum homo-cysteine was inversely related to serum folate in T/T homozygotes at baseline and at the end of folic acid supplementation. These results suggest that folic acid supplementation is needed for infertile women to improve their vitamin status and also to reduce the risk of hyperhomocysteinemia. These effects were different according to their MTHFR C677T genotypes. Therefore, further studies are necessary to determine the optimal level of supplementation of folic acid by MTHFR genotypes.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.3
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• pp.324-328
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• 2006

Carbonic anhydrase III (CA3) is a member of a multigene family that encode carbonic anhydrase isozymes. In this study, a complete coding sequence of the pig CA3 gene which encodes a 260 amino-acid protein was determined. The amino acid comparison showed high sequence similarities with previously identified human (86.5%) CA3 gene and mouse (91.5%) Car3 gene. The partial genomic DNA sequences were also investigated. The length of intron 1 was 727 bp. Comparative sequencing of three pig breeds revealed that there was a T${\rightarrow}$C substitution at position 363 within intron 1. The substitution was situated within a NcoI recognition site and was developed as a PCR-restriction fragment length polymorphism (RFLP) marker for further use in population variation investigations and association analysis. Two alleles (A and B) were identified, and 617 bp fragments were observed for the AA genotype and 236 bp and 381 bp fragments for the BB genotype. The polymorphism of CA3 was detected in 8 pig breeds. Allele B was predominant in the Western pig breeds. In addition, association studies of the CA3 polymorphism with carcass traits in 140 $Yorkshire{\times}Meishan$ $F_2$ offspring showed that the NcoI PCR- RFLP genotype may be associated with variation in several carcass traits of interest for pig breeding. Allele B was associated with increases in lean meat percentage, loin eye height and loin eye area. Statistically significant association with backfat thickness was also found; pigs with the AB genotype had much less backfat thickness than AA or BB genotypes.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.16 no.2
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• pp.152-160
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• 2006

Genotype of ALAD and VDR yields two alleles, respectively and it has been implicated in susceptibility to lead toxicity. Also genotype known to variety by race. To evaluate the genetic susceptibility of ALAD and VDR gene on health effect of lead exposure, this study was done with new workers who entered lead industries from 1992 to 2001. Among database of lead industries of Soonchunhyang University Institute of Industrial Medicine, only new workers were selected for this study. The total of eligible workers for this category was 3,540 workers including non lead exposed workers of same lead industries. Genotype of ALAD and VDR were measured from stored blood in specimen bank of Soonchunhyang University, blood lead and other relevant information were obtained from database of each workers which were gathered at their first year of employment. Among 3,540 new employed study subjects during period of 1992-2001, 3204 workers(90.5%) had ALAD genotype 1-1; whereas 336 workers(9.5%) had variant type of ALAD (1-2 or 2-2). Lead exposed workers, 9.8%(n=243) male and 8.1%(n=16) female were heterozygous for the ALAD allele. Also non lead exposed workers, 8.9%(n=67) male and 9.3%(n=10) female were heterozygous for the ALAD allele. For VDR genotype, 2,903 workers(89.7%) out of total tested 3,238 workers were belonged to type bb and 335 workers(10.3%) were type bB or BB. Lead exposed workers, 10.4%(n=235) male and 12.2%(n=24) female were heterozygous for the VDR allele. Also non lead exposed workers, 9.2%(n=64) male and 12.5%(n=12) female were heterozygous for the VDR allele. No significant differences were seen in mean blood lead levels by ALAD and VDR genotype, nor was significantly associated with blood lead except age in multiple regression analysis.