• BMB Reports
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• 제43권6호
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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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• 제15권18호
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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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• 제14권5호
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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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• 제14권9호
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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.

• 대한치과교정학회지
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• 제44권2호
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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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• 제37권6호
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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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• 제51권4호
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• pp.289-294
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• 2009

본 연구는 한우 inositol 1,4,5-triphosphate receptor type1(IP3R1) 유전자를 대상으로 SNP를 발굴하고, 도체형질과의 관련성 분석을 위하여 수행하였다. PCR 및 염기서열 결정법을 통해 IP3R1 유전자내 3개의 SNP를 발굴하였고, 이중 intron 29에 위치하는 SNP의 경우 미 보고된 신규 SNP로 확인되었다. 발굴된 3개의 SNP를 대상으로 표현형 기록치를 보유한 후대검정우 583두에 대하여 유전자형 분석 및 관련성 분석을 수행하였다. 분석결과 3개의 SNP 중 g.1428617A>G SNP가 생시체중(P<0.05) 및 도체중(P<0.01)과 유의적인 상관관계가 있음을 확인할 수 있었다. 이러한 결과는 추후 한우 개량을 위한 유전자 마커로 활용이 가능할 것으로 판단된다.

• 생명과학회지
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• 제14권2호
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• pp.275-279
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• 2004

사이토카인과 그들 수용체의 유전자 다형성은 면역작용에 의한 질병들의 발병원인에 있어서 유전적인 인자로 여겨지는 후보물질들로서, 자가면역질환 및 염증성 그리고 감염질환에 민감하게 연관되어 있다고 알려져 있다. 최근 새롭게 보고된 Interleukin-29유전자는 유전학적 질병들의 복잡한 특성을 해결할 수 있는 중요한 후보유전자이지만 이 유전자에 대한 다형성에 대한 연구는 아직 보고된바 없다. 우리는 이 연구에서 처음으로 프로모터부분을 포함한 Interleukin-29 유전자의 전체 지름 DNA에서 유전자의 다형성을 염기서열 분석 방법을 이용하여 탐색하였다. Interleukin-29 유전자의 다형성들이 한국인의 알레르기성 비염의 감염력과 관련되어 있는지를 알아보기 위하여 알레르기성 비염환자 및 알레르기성 비염이 걸리지 않은 정상인의 다형성을 유전자형과 대립유전자의 빈도를 비교분석 하였다. 우리는 이 연구에서 사람의 Interleukin-29 유전자의 한 개의 신규의 다형성 (1184C＞A)을 intron 2에서 그리고 한 개의 신규의 변이부위 (-1842_-1841dupGA)를 프로모터에서 찾아냈다. 우리들의 연구 결과는 이들 유전자 다형성 부위 및 변이부위가 알레르기성 비염과 연관은 없는 것으로 밝혀졌다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6227-6232
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• 2012

Interleukin-4 receptor (IL-4R) gene single nucleotide polymorphisms (SNPs) are implicated in cancer development. However, results from the published reports have remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in IL-4R gene and cancer risk. Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) were searched for case-control studies published up to October 30, 2012 that investigated IL-4R polymorphisms and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of any associations. Three IL-4R polymorphisms (Q576R, rs1801275; I75V, rs1805010; S503P, rs1805015) in 21 case-control studies were analyzed. Our meta-analysis indicated that these three polymorphisms are not associated with cancer risk when all studies were pooled together. In the subgroup analysis by tumor site, the results showed that Q576R G allele carriers were associated with a significantly decreased cervical cancer risk (recessive model: OR = 0.77, 95%CI = 0.60-0.98; homozygote comparison: OR = 0.76, 95%CI = 0.58-0.98). I75V G allele carriers were associated with a decreased risk of renal cancer (dominant model = 0.71, 95%CI = 0.57-0.89, heterozygote comparison: OR = 0.69, 95%CI = 0.55-0.87). When stratified by ethnicity, Q576R G allele carriers were associated with a decreased cancer risk in Caucasians (dominant model: OR = 0.90, 95%CI = 0.83-0.98; heterozygote comparison: OR = 0.89, 95%CI = 0.82-0.98). I75V G allele carriers were associated with a decreased cancer risk in Asians (heterozygote comparison: OR = 0.76, 95%CI = 0.62-0.94). S503P C allele carriers were also associated with a decreased cancer risk in Asians (CC VS TT: OR = 0.29, 95%CI = 0.08-0.99). Our results suggest that Q576R, I75V and S503P may be associated with a decreased cancer risk for certain types of cancers and in some specific ethnic groups. Future case-control studies with large sample size are needed to evaluate these associations in detail.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1797-1802
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• 2014

Background: The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation of both genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma (ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to ESCC. Methods: We performed a gene-wide tag SNP-based association study to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthy controls from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highest incidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2 were selected and genotyped using a high-throughput Mass Array genotyping platform. Results: We found a modest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00-3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects with the rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers (CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771 C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI, 0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32-0.85) showed a negative association with ESCC susceptibility. Conclusions: Our results suggest that PTGS2 and PLA2G2A gene polymorphisms may modify the risk of ESCC development.