• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9973-9978
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• 2014

Background: Hypoxia inducible factor-1 alpha (HIF-$1{\alpha}$) is the key regulator of cellular responses to hypoxia and plays a central role in tumour growth. Presence of Single nucleotide polymorphisms (SNPs) in the critical regulatory domains of HIF-$1{\alpha}$ may result in the overexpression of the protein and subsequent changes in the expression of the downstream target genes. The aim of study was to investigate the association of three SNPs (g.C111A, g.C1772T and g.G1790A) of HIF-$1{\alpha}$ with the risk of breast cancer in North Indian sporadic breast cancer patients. Materials and Methods: A total of 400 subjects, including 200 healthy controls and 200 patients with breast cancer were recruited in this study. Genotypes were determined using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. Results: The CC and CA genotype frequency of HIF-$1{\alpha}$ g.C111A polymorphism was 100 vs 99% and 0 vs 1% in breast cancer patients and healthy controls respectively. The frequencies of CC, CT and TT genotype of g.C1772T polymorphism were 76 vs 74.5%, 19 vs 21% and 5 vs 4.5% in breast cancer patients and control individuals respectively. There was no significant difference in genotype and allele frequencies of HIF-$1{\alpha}$ g.C1772T polymorphism between cases and control individuals (p>0.05). For g.G1790A genotypes, all patients and controls had only GG genotype. Conclusions: The three HIF-$1{\alpha}$ polymorphisms (g.C111A, g.C1772T and g.G1790A) are not associated with breast cancer risk in North-West Indian patients.

• Tuberculosis and Respiratory Diseases
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• v.71 no.4
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• pp.254-258
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• 2011

Background: Although the aging process and features of chronic obstructive pulmonary disease (COPD) have several similarities, the relationship between aging and COPD pathogenesis remains incompletely understood. The klotho gene was found to be related to premature aging and emphysematous changes in an animal model. We investigated whether klotho gene polymorphisms are related to COPD susceptibility and emphysema severity. Methods: A total of 219 COPD subjects from the Korean Obstructive Lung Disease Cohort and 305 control subjects were genotyped for two single nucleotide polymorphisms (SNPs) of the klotho gene associated with coronary artery disease. Logistic regression was performed to determine the association of these SNPs with COPD susceptibility and linear regression was performed to investigate their association with emphysema severity in COPD subjects. Results: The mean age of the COPD subjects was 66 years and their mean FEV1 was 1.46 L. There were no associations between either SNP or COPD susceptibility (p=0.6 and 0.2, respectively) and there were no associations with emphysema severity. Conclusion: Genetic polymorphisms of the klotho gene were not associated with COPD in a Korean population.

• BMB Reports
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• v.43 no.6
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• pp.445-449
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• 2010

Aspirin-intolerant asthma (AIA) is characterized by severe asthmatic attack after ingestion of aspirin and/or non-steroidal anti-inflammatory drugs. In this study, we investigated the relationship between Prostaglandin E2 receptor (PTGER) gene family polymorphisms and AIA in 243 AIA patients and 919 aspirin-tolerant asthma (ATA) controls of Korean ethnicity in two separate study cohorts. After genotyping 120 SNPs of the PTGER gene family for the $1^{st}$ cohort study, four SNPs in PTGER1, ten in PTGER3, six in PTGER3, and a haplotype of PTGER2 showed association signals with decreased or increased risk of AIA. Among the positively associated SNPs, one in PTGER1 and four in PTGER3 were analyzed in the $2^{nd}$ cohort study. The results show that rs7543182 and rs959 in PTGER3 retained their effect, although no statistical significance was retained in the $2^{nd}$ cohort study. Our findings provide further evidence that polymorphisms in PTGER3 might play a significant role in aspirin hypersensitivity among Korean asthmatics.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7965-7970
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• 2014

One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2937-2943
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• 2013

Backgrounds: Polymorphisms of OPRM1 A118G and ABCB1 C3435T have been suggested to contribute to inter-individual variability regarding pain sensitivity, opioid usage, tolerance and dependence and incidence of adverse effects in patients with chronic pain. This study aimed to investigate the association of both two polymorphisms with opioid requirements in Chinese patients with cancer pain. Methods: The genotypes of rs1799971 (OPRM1) and rs1045642 (ABCB1) were determined by PCR-RFLP and direct sequencing methods respectively in 112 patients with cancer-related pain. Comparisons between the different genotype or allele groups were performed with t-tests or one-way ANOVA tests, as appropriate. The potential relationship of allele number with opioid response was performed with a trend Jonckheere-Terpstra test. Results: In the 112 subjects, the frequencies of variant 118 G and 3435T allele were 38.4% and 37.9%, respectively. Significant higher 24h-opioid doses were observed in patients with GG (P=0.0004) and AG + GG (P=0.005) genotypes than the AA carriers. The dominant mutant 118G allele tended to be associated with progressively increasing 24h-opioiddoses (P=0.001). Compared with CC/CT, patients with ABCB1 TT genotype received higher 24h- and weight-surface area-adjusted-24h- opioids doses (P=0.057 and 0.028, respectively). Conclusions: The OPRM1 A118G single nucleotide polymorphism (SNP) is a key contributor for the inter-individual variability in opioidrequirements in Chinese cancer pain patients. This may possibly extend to the ABCB1 C3435T SNP.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5415-5420
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• 2013

Background: Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressor gene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a key regulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancers including lung cancer. Methods: We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2 SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female non-smokers. Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotyping assay. Results: The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17-2.06) significantly correlated with an increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also noted for MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27-2.21) compared with the TT genotype. Combined p53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54-4.60) had a supermultiplicative interaction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, and passive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53 or MDM2 mutant alleles. Conclusions: P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or in combination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers.

• The korean journal of orthodontics
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• v.44 no.2
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• pp.96-102
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• 2014

Objective: A recent study suggested that rs6504340, a polymorphism within the homeobox B (HOXB) gene cluster, is associated with the susceptibility for malocclusions in Europeans. The resulting malocclusions require orthodontic treatment. The aim of this study was to investigate the association of rs6504340 and other dentition-implicated polymorphisms with dental and occlusal traits in Korean and Japanese populations. Methods: The study participants included 223 unrelated Koreans from the Busan area and 256 unrelated Japanese individuals from the Tokyo metropolitan area. DNA samples were extracted from saliva specimens. Genotyping for rs6504340 and four single nucleotide polymorphisms (SNPs) that have been shown to be associated with the timing of first tooth eruption and the number of teeth at 1 year of age (rs10506525, rs1956529, rs9674544, and rs8079702) was performed using TaqMan assays. The Index of Orthodontic Treatment Need (IOTN), overjet, overbite, arch length discrepancy, crown sizes, and length and width of the dental arches were measured. Spearman's correlation coefficients were calculated to evaluate relationships between rs6504340 and these dental/occlusal traits. Results: We evaluated the aesthetic components and dental health components of the IOTN in the Korean and Japanese populations and found that neither rs6504340 nor the other four SNPs showed any association with dental and occlusal traits in these East Asian populations. Conclusions: These negative results suggest that further research is needed to identify the genetic determinants of malocclusions in order to reach a consensus.

• BMB Reports
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• v.37 no.6
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• pp.691-699
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• 2004

Osteoporosis is a disease characterized by exaggerated loss of bone mass, with as much as 50 to 85% of the variation in bone mineral density (BMD) commonly accepted as being genetically determined. Although intensive studies have attempted to elucidate the genetic effects of polymorphisms on BMD and/or osteoporosis in several genes, the genes involved are still largely unknown. The possible associations of genetic variants in five-candidate genes (IL10, CCR3, MCP1, MCP2 and GC) with spinal BMD were investigated in Korean postmenopausal women (n = 370). Fourteen SNPs in five candidate genes were genotyped, and the haplotypes of each gene constructed. The associations of adjusted spinal BMD by age, year since menopause (YSM) and body mass index (BMI), with genetic polymorphisms, were analyzed using multiple regression models. Genetic association analysis of Korean postmenopausal women revealed that IL10 -592A > C and/or IL10 ht2 were associated with decreased bone mass, whereas no significant associations were observed with all polymorphisms in other genes. The levels of spinal BMD in individuals bearing the IL10 -592CC genotype were lower ($0.78{\pm}0.16$) than those in others ($0.85{\pm}0.17$) (P = 0.02), and the BMD of IL10 ht2 bearing individuals were also lower ($0.82{\pm}0.15$) than those in others ($0.85{\pm}0.17$) (P = 0.04). Our results suggest that variants of IL10 might play a role in the decreased BMD, although additional study might need to be followed-up in a more powerful cohort.

• Journal of Animal Science and Technology
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• v.51 no.4
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• pp.289-294
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• 2009

Inositol 1,4,5-triphosphate receptor type 1 (IP3R1) is a $Ca^{2+}$ release channel that responds to the second messenger IP3 and that modulates diverse cellular functions such as contraction/excitation, secretion, gene expression and cellular growth. We discovered single nucleotide polymorphisms (SNPs) within IP3R1 gene and analyzed associations between gene polymorphisms and carcass traits in Korean cattle (Hanwoo) in order to develop novel DNA markers at genomic level. Three SNPs were detected at the position of g.1428617A>G, g.1418843C>T and g.1414377C>T with 24 unrelated Hanwoo samples by direct sequencing of the PCR products. We found that genotype of g.1414377C>T SNP was associated with live weight (P<0.05) and carcass weight (P<0.01) using the general linear model of SAS package. These results suggest that polymorphism of IP3R1 gene was associated with weight-related traits in Hanwoo.

• Journal of Life Science
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• v.14 no.2
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• pp.275-279
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• 2004

Gene polymorphisms of cytokines and their receptors are attractive candidates as genetic factors in the pathogenesis of immune-mediated diseases and have been reported to be associated with disease susceptibility to autoimmune, inflammatory and infectious diseases. IL-29 is one of important candidate genes for complex trait of genetic diseases but there is no published survey of single nucleotide polymorphisms (SNPs) in this gene. In this study, for the first time, we have examined the full genomic sequence of IL-29 including the promoter regions to identify SNPs. We examined the frequencies of genotypes and alleles at the SNP site of IL-29 in allergic rhinitis patients and non-allergic rhinitis controls using the direct sequencing method to determine whether this IL-29 SNP is associated with allergic rhinitis in Korean population. We identified one novel SNP (1184C＞A) in the intron 2 and one novel variation site (-1842_-1841dupGA) in the promoter region of human IL-29 gene. The P values of SNP or variation site were not significant between the healthy controls and allergic rhinitis patients. Our results suggest that the 1184C＞A polymorphism and -1842_-1841dupGA variation site in human IL-29 gene were not associated to allergic rhinitis.