• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1057-1060
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• 2016

Background: The tumor suppressor p53 is as a regulator of cell proliferation, apoptosis and many other biological processes as well as external and internal stress responses. Mdm2 SNIP309 is a negative regulator of 53. Therefore, this study aimed to determine the role of the Mdm2 SNIP 309 polymorphism in the gastric mucosal morphological patterns in patients with Helicobacter pylori associated gastritis. Materials and Methods: A prospective cross-sectional study was carried out from November 2014 through November 2015. Biopsy specimens were obtained from patients and infection was proven by positive histology. Gastric mucosa specimens were sent to the Molecular Genetics Unit, Institute of Medicine, Suranaree University of Technology where they were tested by molecular methods to detect the patterns of Mdm2 SNIP 309 polymorphism using the real-time PCR hybridization probe method. The results were analyzed and correlated with gastric mucosal morphological patterns by using C-NBI endoscopy. Results: A total of 300 infected patients were enrolled and gastric mucosa specimens were collected. In this study the percentage of Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygous was 78% and 19 % respectively whereas Mdm2 SNIP309 G/G homozygous was 3%. Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygosity correlated with type 1 to type 3 gastric mucosal morphological patterns (P<0.01) whereas Mdm2 SNIP309 G/G homozygous correlated with type 4 and type 5 (P<0.01). Conclusions: Our study finds the frequency of Mdm2 SNIP309 G/G in a Thai population is very low, and suggests that this can explain ae Thailand enigma. Types 1 to type 3 are the most common gastric mucosal morphological patterns according to the unique genetic polymorphism of MDM2 SNIP 309 in the Thai population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3931-3936
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• 2012

Background: Epidemiological studies evaluating the association of two variants rs9340799 and rs2234693 on estrogen receptor 1 (ESR1) with prostate risk have generated inconsistent results. Methods: A meta-analysis was here conducted to systematically evaluate the relationship of these two variants with prostate cancer susceptibility. Results: For rs9340799, heterozygosity of T/C carriers showed a significant increased prostate cancer risk with a pooled odds ratio (OR) of 1.34 (95% CI = 1.06-1.69) while homozygote C/C carriers showed an increased but not statistically significant association with prostate cancer risk (pooled OR = 1.29, 95% CI = 0.94-1.79). Compared to the homozygous TT carriers, the allele C carriers showed a 31% increased risk for prostate cancer (pooled OR = 1.31, 95% CI = 1.06-1.63). No significant association between the rs2234693 and prostate cancer risk was found with the pooled OR of 1.15 (95% CI = 0.97-1.39, T/C and C/C vs. T/T) under the dominant genetic model. Compared to the homozygote T/T carriers, the heterozygous T/C carriers did not show any significantly different risk of prostate cancer (pooled OR = 1.13, 95% CI = 0.94-1.36) and the homozygous C/C carriers also did not show a significant change for prostate cancer risk compared to the wide-type T/T carriers (pooled OR = 1.26, 95% CI = 0.98-1.62). Conclusion: These data suggested that variant rs9340799, but not rs2234693, on ESR1 confers an elevated risk of prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7589-7595
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• 2014

Apurinic/apyrimidinic endonuclease 1 (APEX1) is a multifunctional protein which plays a central role in the BER pathway. APEX1 gene being highly polymorphic in cancer patients and has been indicated to have a contributive role in Apurinic/apyrimidinic (AP) site accumulation in DNA and consequently an increased risk of cancer development. In this case-control study, all exons of the APEX1 gene and its exon/intron boundaries were amplified in 530 breast cancer patients and 395 matched healthy controls and then analyzed by single-stranded conformational polymorphism followed by sequencing. Sequence analysis revealed fourteen heterozygous mutations, seven 5'UTR, one 3'UTR, two intronic and four missense. Among identified mutations one 5'UTR (rs41561214), one 3'UTR (rs17112002) and one missense mutation (Ser129Arg, Mahjabeen et al., 2013) had already been reported while the remaining eleven mutations. Six novel mutations (g.20923366T>G, g.20923435G>A, g.20923462G>A, g.20923516G>A, 20923539G>A, g.20923529C>T) were observed in 5'UTR region, two (g.20923585T>G, g.20923589T>G) in intron1 and three missense (Glu101Lys, Ala121Pro, Ser123Trp) in exon 4. Frequencues of 5'UTR mutations; g.20923366T>G, g.20923435G>A and 3'UTR (rs17112002) were calculated as 0.13, 0.1 and 0.1 respectively. Whereas, the frequency of missense mutations Glu101Lys, Ser123Trp and Ser129Arg was calculated as 0.05. A significant association was observed between APEX1 mutations and increased breast cancer by ~9 fold (OR=8.68, 95%CI=2.64 to 28.5) with g.20923435G>A (5'UTR), ~13 fold (OR= 12.6, 95%CI=3.01 to 53.0) with g.20923539G>A (5'UTR) and~5 fold increase with three missense mutations [Glu101Lys (OR=4.82, 95%CI=1.97 to 11.80), Ser123Trp (OR=4.62, 95%CI=1.7 to 12.19), Ser129Arg (OR=4.86, 95%CI=1.43 to 16.53)]. The incidence of observed mutations was found higher in patients with family history and with early menopause. In conclusion, our study demonstrates a significant association between germ line APEX1 mutations and breast cancer patients in the Pakistani population.

• Korean Journal of Plant Tissue Culture
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• v.24 no.4
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• pp.239-256
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• 1997

Plants belonging to the category of 2n apomixis or agamospermy form embryos and seeds without the processes of normal meiosis and syngamy. Seeds produced in this way have identical genotype of their maternal parent. Three different types of agamospermy are recognized: diplospory, apospory, and adventitious (adventive) embryony. $F_1$ hybrid cultivars cannot be used as seed sources in the next ($F_2$) generation because this generation would be extremely variable as a result of genetic segregation. Hybrid vigor is also reduced in the $F_2$ generation. Therefore, parental stocks for hybrid seed production need to be maintained and cross must be continuously repeated. Agamospermic 2n apomixis would make it possible to fix the genotype of a superior variety so that clonal seeds faithfully representing that genotype could be continuously and cheaply produced independent of pollination. That is, $F_1$ hybrid seeds could be produced for many generations without loss of vigor or genotype alteration. Production of apomictic $F_1$ hybrid seed would be simplified because line isolation would not be necessary to produce seed or to maintain parental lines, and the use of male-sterile lines could be avoided. Overall, apomixis would enable a significant reduction in hybrid seed production costs. Additionally, the production of clonal seed is not only important for seed propagated crops, but also for the propagation of heterozygous fruit trees and timbers. Clonal seed would help avoid costly and time-consuming vegetative propagating methods that are currently used to ensure the large-scale production of these plants. Apomixis is scattered throughout the plant kingdom, but few important agricultural crops possess this trait Therefore, most research to date has centered on introgressing the trait of apomixis into agricultural crops such as wheat, maize, and some forage grasses from wild distant relatives by traditional cross breeding. The classical breeding approach, however is slow and often impeded by many breeding barriers. These problems could be surmounted by taking mutagenesis or molecular approach. Arabidopsis thaliana is a tiny sexually reproducing plant and is convenient in constructing and screening in molecular researches. Male-sterile mutants of Arabidopsis are particularly suitable genetic background for mutagenesis and screening for apomictic mutants. Molecular approaches towards isolating the genes controlling the apomictic process are feasible. Direct isolation of genes conferring apomixis development would greatly facilitate the transfer of this trait to wide variety of crops. Such studies are now in progress.

• Journal of Veterinary Clinics
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• v.32 no.1
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• pp.1-4
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• 2015

This study was performed to survey prevalence of Copper metabolism domain containing 1 (COMMD1) mutation using molecular diagnostic method in a population of Bedlington terriers in Korea. COMMD1 gene (formerly MURR1) functions as a regulator of sodium transport and copper metabolism. The deletion of exon 2 of the COMMD1 gene causes copper toxicosis in Bedlington terriers. Bedlington terriers with this autosomal recessive disorder were shown to have the elevated liver copper levels due to genetic derangement in the biliary copper excretion pathway. DNA samples were extracted from whole blood collected from 257 Bedlington terriers (109 males, 148 females) of pet dog clubs in Korea. A multiplex PCR was carried out to detect of exon 2 deletion of COMMD1 gene. In this study, it was possible to know the existence and prevalence of exon 2 deletion of COMMD1 in Bedlington terriers in Korea. Of the 257 samples, 131 (51%) were wild type homozygous for the normal COMMD1 gene, 108 (42%) were heterozygous, having both normal and mutated copy of the COMMD1 gene. The eighteen (7%) were mutant type homozygous. The results of genetic analysis could help establish proper management strategy and selective breeding program to prevent COMMD1 mutation in Bedlington terriers in Korea.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3705-3713
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• 2014

E-Cadherin (CDH1) genetic variations may be involved in invasion and metastasis of various cancers by altering gene transcriptional activity of epithelial cells. However, published studies on the association of CDH1 gene polymorphisms and cancer risk remain contradictory, owing to differences in living habits and genetic backgrounds. To derive a more better and comprehensive conclusion, the present meta-analysis was performed including 57 eligible studies of the association between polymorphisms of CDH1 gene promoter -160 C>A, -347 G>GA and 3'-UTR +54 C>T and cancer risk. Results showed that these three polymorphisms of CDH1 were significantly associated with cancer risk. For -160 C>A polymorphism, -160A allele carriers (CA and CA+AA) had an increased risk of cancer compared with the homozygotes (CC), and the similar result was discovered for the -160A allele in the overall analyses. In the subgroup analyses, obvious elevated risk was found with -160A allele carriers (AA, CA, CA+AA and A allele) for prostate cancer, while a decreased colorectal cancer risk was shown with the AA genotype. For the -347 G>GA polymorphism, the GAGA genotype was associated with increased cancer risk in the overall analysis with homozygous and recessive models. In addition, results of subgroup analysis indicated that the elevated risks were observed in colorectal cancer and Asian descendants. For +54 C>T polymorphism, a decreased risk of cancer was found in heterozygous, dominant and allele models. Moreover, +54T allele carriers (CT, CT+TT genotype and T allele) showed a potential protective factor in gastric cancer and Asian descendants.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.889-896
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• 2015

Matrix metalloproteinase-2 (MMP2) is an endopeptidase, mainly responsible for degradation of extracellular matrix components, which plays an important role in cancer disease. A single nucleotide polymorphism (SNP) at -1306 disrupts a Sp1-type promoter site. The results from the published studies on the association between MMP2 -1306 C>T polymorphism and cancer risk are contradictory and inconclusive. In the present study, a meta-analysis was therefore performed to evaluate the strength of any association between the MMP2 -1306 C>T polymorphism and risk of cancer. We searched all eligible studies published on association between MMP2 -1306 C>T polymorphism and cancer risk in PubMed (Medline), EMBASE and Google Scholar online web databases until December 2013. Genotype distribution data were collected to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) to examine the strength of the association. A total of 8,590 cancer cases and 9,601 controls were included from twenty nine eligible case control studies. Overall pooled analysis suggested significantly reduced risk associated with heterozygous genotype (CT vs CC: OR=0.758, 95%CI=0.637 to 0.902, p=0.002) and dominant model (TT+CT vs CC: OR=0.816, 95%CI=0.678 to 0.982, p=0.032) genetic models. However, allelic (T vs C: OR=0.882, 95%CI=0.738 to 1.055, p=0.169), homozygous (TT vs CC: OR=1.185, 95%CI=0.825 to 1.700, p=0.358) and recessive (TT vs CC+CT: OR=1.268, 95%CI=0.897 to 1.793, p=0.179) models did not show any risk. No evidence of publication bias was detected during the analysis. The results of present meta-analysis suggest that the MMP2 -1306 C>T polymorphism is significantly associated with reduced risk of cancer. However, further studies with consideration of different populations will be required to evaluate this relationship in more detail.

• Clinical and Experimental Pediatrics
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• v.57 no.1
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• pp.50-53
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• 2014

Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or familial) or secondary form (acquired). The familial form of HLH (FHL) is a potentially fatal autosomal recessive disorder that occurs because of constitutional defects in cell-mediated cytotoxicity. Here, we report a fatal neonatal case of type 2 FHL (FHL2) that involved a novel frameshift mutation. Clinically, the newborn presented with severe sepsis-like features and required mechanical ventilation and continuous venovenous hemodiafiltration. Flow cytometry analysis showed marked HLH and complete absence of intracytoplasmic perforin expression in cytotoxic cells; therefore, we performed molecular genetic analyses for PRF1 mutations, which showed that the patient had a compound heterozygous mutation in PRF1, that is, c.65delC ($p.Pro22Argfs^*2$) and c.1090_1091delCT ($p.Leu364Glufs^*93$). Clinical and genetic assessments for FHL are required for neonates with refractory fever and progressive multiple organ failure, particularly when there is no evidence of microbiological or metabolic cause.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.49-52
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• 2016

X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Bruton's tyrosine kinase (BTK ) gene mutations. These mutations cause defects in B-cell development, resulting in the virtual absence of these lymphocytes from the peripheral circulation. Consequently, this absence leads to a profound deficiency of lg all isotypes, and an increased susceptibility to encapsulated bacterial infections. A 15-month-old Korean boy presented with recurrent sinusitis and otitis media after 6 months of age, and had a family history of 2 maternal uncles with XLA. Laboratory tests revealed a profound deficiency of Ig isotypes, and a decreased count of $CD19^+$ B cells in the peripheral circulation. Based on his family history and our laboratory test results, he was diagnosed with XLA. We performed BTK gene analysis of peripheral blood samples obtained from family members to confirm the diagnosis. Mutational analysis revealed a novel hemizygous frameshift mutation (c.82delC, p.Arg28Alafs*5), in the BTK gene. His mother and maternal grandmother were heterozygous carriers of this mutation and his two maternal uncles were hemizygous at the same position. After XLA diagnosis, intravenous immunoglobulin (400 mg/kg, monthly) treatment was initiated; recurrent sinusitis and otitis media were subsequently brought under control. To our knowledge, this is the first reported case of a Korean pedigree with a novel mutation in the BTK gene.

• Asian-Australasian Journal of Animal Sciences
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• v.17 no.4
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• pp.560-563
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• 2004

The study was undertaken to evaluate the effect of naked neck gene on mortality, cell mediated and humoral immune response in white plumage broiler population. The mortality of homozygous naked neck (Na/Na) broilers (11.71%) was comparatively lower than that of heterozygous naked neck (Na/na) (12.28%) and normally feathered (na/na) (13.59%) broilers. The humoral immune response was measured against (1% v/v) sheep red blood cells (SRBC) for total haemagglutinin (HA) antibody, 2-mercaptoethanol resistance (MER) or (IgG) antibody and 2-mercaptoethanol sensitive (MES) or (IgM) antibody titre on 7 days post-immunization. The titre was expressed as log2 of the highest dilution which shows complete haemagglutination. Total HA titers of Na/Na and Na/na (11.05$\pm$0.53 and 11.09$\pm$0.38) were comparatively higher than that of na/na (10.26$\pm$0.42). The MES antibody titre of Na/Na (8.50$\pm$0.53) and Na/na (7.63$\pm$0.45) broilers were significantly higher as compared to na/na (6.11$\pm$0.32) broilers. The MER titre of na/na genetic group (4.15$\pm$0.42) was significantly higher than Na/Na (2.55$\pm$0.37) and comparatively higher than Na/na (3.45$\pm$0.38) broilers. In vivo cell response to phytohaemagglutinin-P (PHA-P), measured as Foot Index (FI) in mm expressed significantly higher response in Na/na (0.473$\pm$0.05) and Na/Na (0.413$\pm$0.04) broilers as compared to na/na (0.304$\pm$0.03) broilers. The result of present study suggested that white plumage naked neck broilers had better immune response as compared to normally feathered broilers.