• Asian-Australasian Journal of Animal Sciences
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• v.33 no.9
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• pp.1378-1386
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• 2020

Objective: Chinese indigenous sheep breeds can be classified into the following three categories by their tail morphology: fat-tailed, fat-rumped and thin-tailed sheep. The typical sheep breeds corresponding to fat-tailed, fat-rumped, and thin-tailed sheep are large-tailed Han, Altay, and Tibetan sheep, respectively. Detection of copy number variation (CNV) and selection signatures provides information on the genetic mechanisms underlying the phenotypic differences of the different sheep types. Methods: In this study, PennCNV software and F-statistics (F_ST) were implemented to detect CNV and selection signatures, respectively, on the X chromosome in three Chinese indigenous sheep breeds using ovine high-density 600K single nucleotide polymorphism arrays. Results: In large-tailed Han, Altay, and Tibetan sheep, respectively, a total of six, four and 22 CNV regions (CNVRs) with lengths of 1.23, 0.93, and 7.02 Mb were identified on the X chromosome. In addition, 49, 34, and 55 candidate selection regions with respective lengths of 27.49, 16.47, and 25.42 Mb were identified in large-tailed Han, Altay, and Tibetan sheep, respectively. The bioinformatics analysis results indicated several genes in these regions were associated with fat, including dehydrogenase/reductase X-linked, calcium voltage-gated channel subunit alpha1 F, and patatin like phospholipase domain containing 4. In addition, three other genes were identified from this analysis: the family with sequence similarity 58 member A gene was associated with energy metabolism, the serine/arginine-rich protein specific kinase 3 gene was associated with skeletal muscle development, and the interleukin 2 receptor subunit gamma gene was associated with the immune system. Conclusion: The results of this study indicated CNVRs and selection regions on the X chromosome of Chinese indigenous sheep contained several genes associated with various heritable traits.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3461-3464
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• 2012

Methotrexate (MTX) is an important drug for the treatment of childhood acute lymphoblastic leukemia (ALL). However, related toxicity occurs in many organs which may cause interruption of treatment, morbidity, and mortality. Single nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus affect the metabolism of MTX and influence the effectiveness. Therefore, we hypothesized that genetic variations of DHFR and GGH genes may influence the risk of toxicity after high dose MTX. The study population comprised of 105 children with ALL who were treated according to the modified St Jude Total XV protocol. The patients received 2.5 or $5g/m^2$ of MTX for 5 doses during the consolidation phase. Genotyping of DHFR 829C>T and GGH-401C>T was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The GGH-401CT and TT genotypes were associated with increased risk of leukopenia and thrombocytopenia after high dose MTX (OR 2.97, 95%CI; 1.24-7.13 and OR 4.02, 95%CI; 1.58-10.26). DHFR 829C>T was not associated with toxicity. In conclusion, the GGH-401CT and TT genotypes were found to increase the risk of severe leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3667-3673
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• 2014

Background: colorectal cancer (CRC) is the third most common type of cancers and the fourth leading cause of death worldwide. In Saudi Arabia, CRC accounts for 8.5% of all tumors; it ranks first among all cancers in males and third among females. The aim of this study was to link between different PARP-1 mutations and risk of CRC in Saudi population and to determine common variants of PARP-1 in Saudi CRC patients and normal individuals. Materials and Methods: DNA samples were isolated from fifty CRC patients and from a comparable number of control subjects then sequenced to detect different variations present in exons 3, 17, and 21 of the PARP-1 gene. Results and Conclusions: When comparing the genotype and allele frequencies of all detected SNPs in CRC patients with those in controls, we found none were significantly different for all variants even the most common SNP in PARP-1 gene (Val762Ala). However, two novel alterations in exon 21 were found to be associated with increased risk of CRC. The variants identified as (1) Lys933Asn [p-value 0.0318] and (2) Lys945Asn [p-value 0.0257]. Our results suggest that PARP-1 Lys933Asn and Lys945Asn alterations could be associated with increased risk of CRC in the Saudi population.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1925-1931
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• 2016

Background: The XRCC1 protein facilitates various DNA repair pathways; single-nucleotide polymorphisms (SNPs) in this gene are associated with a risk of gastrointestinal cancer (GIC) with inconsistent results, but no data have been previously reported for the Sabah, North Borneo, population. We accordingly investigated the XRCC1 Arg194Trp and Arg399Gln SNPs in terms of GIC risk in Sabah. Materials and Methods: We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reaction-restriction fragment length polymorphism approach. We validated heterozygosity and homozygosity for both SNPs using direct sequencing. Results: The presence of a variant 194Trp allele in the Arg194Trp SNP was significantly associated with a higher risk of GIC, especially with gastric and colorectal cancers. We additionally found that the variant 399Gln allele in Arg399Gln SNP was associated with a greater risk of developing gastric cancer. Our combined analysis revealed that inheritance of variant alleles in both SNPs increased the GIC risk in Sabah population. Based on our etiological analysis, we found that subjects ${\geq}50years$ and males who carrying the variant 194Trp allele, and Bajau subjects carrying the 399Gln allele had a significantly increased risk of GIC. Conclusions: Our findings suggest that inheritance of variant alleles in XRCC1 Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2157-2162
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• 2012

Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3391-3394
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• 2016

Background: Helicobacter pylori is now recognized as a causative factor of chronic gastritis, gastroduodenal ulcers, gastric cancer and mucosa-associated lymphatic tissue lymphoma. Toll-like receptors are important bacterial receptors in gastric epithelial cell signaling transduction and play critical roles in gastric carcinogenesis. Materials and Methods: A total of 400 patients undergoing esophagogastroduodenoscopy for investigation of chronic abdominal pain were genotyped for single-nucleotide polymorphisms (SNPs) in TLR1 (rs4833095) using TagMan SNPs genotyping assay by real-time PCR hybridization. Relationships with susceptibility to H. pylori infection and pre-malignant gastric mucosa morphological patterns, classified by magnifying NBI endoscopy, were investigated. Results: The percentages of TLR1 rs4833095, CC homozygous, CT heterozygous and TT homozygous cases were 34, 46.5 and 19%, respectively. CC showed statistical differences between H. pylori positive and negative cases (P<0.001). CT and TT correlated with type 1 and type 2 gastric mucosal morphological patterns (P <0.01) whereas CC correlated with types 3 and 4 (P<0.01). Conclusions: This study demonstrated good correlation of TLR1 rs4833095 genotype with severity of inflammation in H. pylori infected gastric mucosa according to gastric mucosal morphologic patterns with magnifying NBI endoscopy.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.1
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• pp.12-23
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• 2020

Objective: The objective of a conservation program is to maintain maximum genetic diversity and preserve the viability of a breed. However, the efficiency of a program is influenced by the ability to accurately measure and predict genetic diversity. Methods: To examine this question, we conducted a simulation in which common measures (i.e. heterozygosity) and novel measures (identity-by-descent probabilities and parental genomic components) were used to estimate genetic diversity within a conserved population using double-labeled single nucleotide polymorphism markers. Results: The results showed that the accuracy and sensitivity of identity-by-state probabilities and heterozygosity were close to identity by descent (IBD) probabilities, which reflect the true genetic diversity. Expected heterozygosity most closely aligned with IBD. All common measures suggested that practices used in the current Chinese pig conservation program result in a ~5% loss in genetic diversity every 10 generations. Parental genomic components were also analyzed to monitor real-time changes in genomic components for each male and female ancestor. The analysis showed that ~7.5% of male families and ~30% of female families were lost every 5 generations. After 50 generations of simulated conservation, 4 male families lost ~50% of their initial genomic components, and the genomic components for 24.8% of the female families were lost entirely. Conclusion: In summary, compared with the true genetic diversity value obtained using double-labeled markers, expected heterozygosity appears to be the optimal indicator. Parental genomic components analysis provides a more detailed picture of genetic diversity and can be used to guide conservation management practices.

• Biomedical Science Letters
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• v.18 no.4
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• pp.377-383
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• 2012

Recent genome-wide association studies (GWAS) have identified a number of common variants associated with blood pressure homeostasis and hypertension in population. In the previous study, single nucleotide polymorphisms (SNPs) in the SLC4A4 gene have been reported to be associated with hypertension in Han Chinese population. We aimed to confirm whether the genetic variation of SLC4A4 gene influence the susceptibility to blood pressure and hypertension in Korean population. We genotyped variants in or near SLC4A4 in a population-based cohort including 7,551 unrelated Korean from Ansan and Ansung. Here, we performed association analysis to elucidate the possible relations of genetic polymorphisms in SLC4A4 gene with blood pressure traits. By examining genotype data of a total of 7,551 subjects in the Korean Association REsource (KARE) study, we discovered the SLC4A4 gene polymorphisms are associated with blood pressure and hypertension. The common and highest significant polymorphism was rs6846301 (${\beta}$=0.839, additive P=0.032) with systolic blood pressure (SBP), rs6846301 (${\beta}$=0.588, additive P=0.027) with diastolic blood pressure (DBP), and rs6846301 (OR=1.23, CI: 1.09~1.40, additive $P=1.2{\times}10^{-3}$) with hypertension. Furthermore, the SNP rs6846301 was consistently associated with both blood pressure and hypertension. Consequently, we found statistically significant SNPs in SLC4A4 gene that are associated with both blood pressure and hypertension traits. In addition, these results suggest that the individuals with the minor alleles of the SNP in the SLC4A4 gene may be more susceptible to the development of hypertension in the Korean population.

• Biomedical Science Letters
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• v.19 no.4
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• pp.338-343
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• 2013

Serum levels of alkaline phosphatase (ALP) are widely used in the clinical diagnosis of hepatic diseases and the assessment of liver status. They also have epidemiological significance to be prospective risk factors for bone diseases, such as osteitis deformans, rickets, osteomalacia, hyperparathyroidism, healing fractures, and osteoblastic bone tumors. In the previous study, single nucleotide polymorphisms (SNPs) in several genes have been reported to be associated with serum levels of liver enzyme in American population. We aimed to confirm whether the genetic variation of RETNLB (resistin like beta) gene also influence the serum levels of liver enzyme in Korean population. We genotyped variants in or near RETNLB in a population-based sample including 994 Korean adults. Here, we performed association analysis to elucidate the possible relations of genetic polymorphisms in RETNLB gene with serum levels of liver enzyme. By examining genotype data of a total of 944 subjects in 5 hospital health promotion centers, we discovered the RETNLB gene polymorphisms are associated with serum levels of ALP. The common and highest significant polymorphism was rs736327 (${\beta}$=8.66, P=2.37E-05), rs7639070 (${\beta}$=8.56, P=3.24E-05) with ALP in all groups. Furthermore, the ALP was consistently associated with rs736327 (${\beta}$=10.40, P=5.23E-05), rs7639070 (${\beta}$=10.32, P=6.74E-05) in the male population. Consequently, we found statistically significant SNPs in RETNLB gene that are associated with serum levels of ALP. In addition, these results suggest that the individuals with the minor alleles of the SNP in the RETNLB gene may have elevated serum levels of ALP in the Korean population.

• The Journal of Korean Society of Virology
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• v.30 no.1
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• pp.29-37
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• 2000

The aim of this study was to investigate viral etiology in dilated cardiomyopathy (DCM) by polymerase chain reaction (PCR) or nested reverse transcription PCR (RT-PCR), and characterize the enteroviral RNA presented in the clinical specimens. Twenty-eight paraffin-embedded heart tissue samples were assayed to detect cytomegalovirus, herpes simplex virus type 1, type 2, parvovirus, adenovirus, and enterovirus (EV) with each specific primer. Of these 28 patients (mean age: 27, M: 24, F: 4), 26 were histologically diagnosed as DCM and 2 as myocardial infarction (MI). Nested RT-PCR detected enteroviral RNA in 7 (26.9%) of 26 patients with DCM, and none of patients with MI. And none of DNA viruses tested were detected from the samples. Amplified products were also genotyped by single-strand conformation polymorphism (SSCP). Three subtypes can be differentiated from 7 clinical specimens. Furthermore, direct sequence analysis was performed to determine whether genetic variation of EV is present in the explanted heart tissues from patients with DCM. Although most of the sequences among the wild isolates have the greatest similarity to those of coxsackievirus B3, there are specific regions of variable sequences (no 490 - no 510). The data suggest that enterovirus may be a major viral pathogen for the DCM in Korea and nucleotide sequence data indicate that coxsackievirus B3 may be a leading etiologic agent of DCM.