• Title, Summary, Keyword: genetic polymorphisms

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Common MCL1 polymorphisms associated with risk of tuberculosis

  • Shin, Hyoung-Doo;Cheong, Hyun-Sub;Park, Byung-Lae;Kim, Lyoung-Hyo;Han, Chang-Su;Lee, In-Hee;Park, Seung-Kyu
    • BMB Reports
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    • v.41 no.4
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    • pp.334-337
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    • 2008
  • MCL1 expression has been found to be up-regulated during infection with virulent Mycobacterium tuberculosis. We investigated the genetic polymorphisms in MCL1 as potential candidate gene for a host genetic study of clinical TB infection. We have sequenced exons and their boundaries of MCL1, including the 1.5 kb promoter region, to identify polymorphisms, and eight polymorphisms were identified. The genetic associations of polymorphisms in MCL1 with clinical TB patients (n=486) and normal controls (n=370) were analyzed. Using statistical analyses, one common promoter polymorphism (MCL1-324C>A) which is absolutely linked with three other SNPs in the promoter and 3'UTR regions, were found to be significantly associated with increased risk of clinical TB disease. The frequency of the A-bearing genotype of -324C>A was higher in clinical TB patients than in normal controls (P=0.0008, OR=1.68). Our findings suggest that polymorphisms in MCL1 might be one of genetic factors for the risk of clinical tuberculosis development.

Meta-analysis of Association Studies of CYP1A1 Genetic Polymorphisms with Digestive Tract Cancers Susceptibility in Chinese

  • Liu, Chang;Jiang, Zheng;Deng, Qian-xi;Zhao, Ya-nan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4689-4695
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    • 2014
  • Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and Methods: Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed-effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Results: Eighteen case-control studies with 1,747 cases and 2,923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinese populations. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

Muscle-Specific Creatine Kinase Gene Polymorphisms in Korean Elite Athletes

  • Kang, Byung-Yong;Kang, Chin-Yang;Lee, Kang-Oh
    • Toxicological Research
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    • v.19 no.2
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    • pp.115-121
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    • 2003
  • In view of the importance of muscle-specific creatine kinase (CKMM) gene as a genetic factor for athletic performance, we investigate the relationship between elite athletic performance and two restriction fragment length polymorphisms (Ncol and Taql RFLPs) in the CKMM gene. Genomic DNA was extracted from white blood cells of 98 unrelated male Korean elite athletes and 04 sedentary controls, respectively. Two genetic polymorphisms in the CKMM gene were detected by the polymerase chain reaction and the digestion with restriction endonucleases, Ncol and Taql, respectively. There were no significant associations between two genetic polymorphisms in the CKMM gene and elite athletic performance or clinical parameters in our subjects. Therefore, these findings suggest that two genetic polymorphisms in the CKMM gene may not be useful as genetic markers to predict the athletic performance in male Koreans.

GENETIC POLYMORPHISMS OF THE GLUTATHIONE S-TRANSFERASE AND CYP1A1 GENES IN KOREAN ORAL SQUAMOUS CELL CARCINOMA (한국인 구강 편평세포암에서 Glutathione S-transferase와 CYP1A1 유전자의 다형성)

  • Cha, In-Ho;Kwon, Jong-Jin;Park, Kwang-Kyun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.28 no.5
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    • pp.364-371
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    • 2002
  • Many chemical compopunds are converted into reactive electrophilic metabolites by the oxidative(Phase I) enzymes, which are mainly cytochrome P-450 enzyme(CYPs). Phase II conjugating enzymes, such as glutathione S-transferase(GST), usually act as inactivation of enzymes. Genetic polymorphisms have been found to be associated with increased susceptibility to cancer of the lung, bladder, breast and colorectal. Many of the polymorphic genes of carcinogen metabolism show considerably different type of cancer among different ethnic groups as well as individuals within the same group. The aim of this study is (1) to establish the frequencies of genetic polymorphisms of GSTM1 and CYP1A1 in Korean oral squamous cell carcinoma(SCC), (2) to associate oral SCC with the risk of these genetic polymorphisms. The genetic polymorphisms of the GSTM1 and the CYP1A1 genes among 50 Korean oral SCC were analyzed using polymerase chain reaction(PCR). The results suggest that the homozygote and the mutant type of CYP1A1 MspI polymorphisms may be associated with genetic susceptibility to oral SCC in Korean. A combination of the GSTM1 null type with the homozygote(m1/m1), and the mutant(m2/m2) type of CYP1A1 MspI polymorphisms showed a relatively high risk of oral SCC in Korean. In the smoking group, the GSTM1 wild genotype may be the high risk factor of oral SCC in Korean. These data coincide with the hypothesis which states that different susceptibility to cancer of genetic polymorphisms exist among different ethnic group and different types of human cancer.

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

  • Guo, Cheng-Xian;Yang, Guo-Ping;Pei, Qi;Yin, Ji-Ye;Tan, Hong-Yi;Yuan, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.713-718
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    • 2015
  • Background: A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients.

CYP1A1 Gene Polymorphisms: Modulator of Genetic Damage in Coal-Tar Workers

  • Giri, Shiv Kumar;Yadav, Anita;Kumar, Anil;Dev, Kapil;Gulati, Sachin;Gupta, Ranjan;Aggarwal, Neeraj;Gautam, Sanjeev Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3409-3416
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    • 2012
  • Aim: It is well known that polycyclic aromatic hydrocarbons (PAHs) such as benzo (a) pyrene have carcinogenic properties and may cause many types of cancers in human populations. Genetic susceptibility might be due to variation in genes encoding for carcinogen metabolizing enzymes, such as cytochrome P-450 (CYP450). Our study aimed to investigate the effect of genetic polymorphisms of CYP1A1 (m1 and m2) on genetic damage in 115 coal-tar workers exposed to PAHs at their work place. Methods: Genetic polymorphisms of CYP1A1 were determined by the PCR-RFLP method. Comet and buccal micronucleus assays were used to evaluate genetic damage among 115 coal tar workers and 105 control subjects. Results: Both CYP1A1 m1 and CYP1A1 m2 heterozygous and homozygous (wt/mt+mt/mt) variants individually as well as synergistically showed significant association (P<0.05) with genetic damage as measured by tail moment (TM) and buccal micronuclei (BMN) frequencies in control and exposed subjects. Conclusion: In our study we found significant association of CYP1A1 m1 and m2 heterozygous (wt/mt)+homozygous (mt/mt) variants with genetic damage suggesting that these polymorphisms may modulate the effects of PAH exposure in occupational settings.

Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion, Extranodal Extension, and Lower Disease-Free Survival in Thai Breast Cancer Patients

  • Sa-Nguanraksa, Doonyapat;Suntiparpluacha, Monthira;Kulprom, Anchalee;Kummalue, Tanawan;Chuangsuwanich, Tuenjai;Avirutnan, Panissadee;O-Charoenrat, Pornchai
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2935-2940
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    • 2016
  • Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.

Comprehensive Assessment of Associations between ERCC2 Lys751Gln/Asp312Asn Polymorphisms and Risk of Non-Hodgkin Lymphoma

  • Zhou, Jue-Yu;He, Li-Wen;Liu, Jie;Yu, Hai-Lang;Wei, Min;Ma, Wen-Li;Shi, Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9347-9353
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    • 2014
  • Background: Excision repair crossing-complementing group 2 (ERCC2), also called xeroderma pigmentosum complementary group D (XPD), plays a crucial role in the nucleotide excision repair (NER) pathway. Previous epidemiological studies have reported associations between ERCC2 polymorphisms and non-Hodgkin lymphoma (NHL) risk, but the results have remained controversial. Materials and Methods: We conducted this meta-analysis based on eligible case-control studies to investigate the role of two ERCC2 polymorphisms (Lys751Gln and Asp312Asn) in determining susceptibility to NHL. Ten case-control studies from several electronic databases were included in our study up to August 14, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models to estimate the association strength. Results: The combined results based on all studies did not show any association between Lys751Gln/Asp312Asn polymorphisms and NHL risk for all genetic models. Stratified analyses by histological subtype and ethnicity did not indicate any significant association between Lys751Gln polymorphism and NHL risk. However, a significant reduced risk of NHL was found among population-based studies (Lys/Gln versus Lys/Lys: OR=0.87, 95% CI=0.77-0.99, P=0.037) but not hospital-based studies. As for Asp312Asn polymorphism, there was no evidence for the association between this polymorphism and the risk of NHL in all subgroup analyses. Conclusions: This meta-analysis suggests that there may be no association between Lys751Gln/Asp312Asn polymorphism and the risk of NHL and its two subtypes, whereas ERCC2 Lys751Gln heterozygote genotype may provide protective effects against the risk of NHL in population-based studies. Therefore, large-scale and well-designed studies are needed to clarify the effects of haplotypes, gene-gene, and gene-environment interactions on these polymorphisms and the risk of NHL and its different histological subtypes in an ethnicity specific population.

The Distributions of Three Genetic Polymorphisms in the Estrogen $Receptor-\alpha$ Gene in Korean Essential Hypertensives (한국인 본태성 고혈압군에서 에스트로젠 수용체-$\alpha$(유전자에 존재하는 다형성의 분포에 관한 연구)

  • Kim Ji Young;Kang Byung Yong;Lee Kang Oh
    • Environmental health and toxicology
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    • v.20 no.3
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    • pp.249-258
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    • 2005
  • Blood pressure, obesity and bone mineral density are multifactorial traits influenced by genetic factor. The purpose of this study was to clarify the association between three genetic polymorphisms in the estrogen receptor-$\alpha$ (ER -$\alpha$) gene and essential hypertension in korean population. One hundred and seventy-one people including 90 normotensives and 81 essential hypertentives were recruited. Among genetic polymorphisms studied, the Xba I RFLP in the intron 1 of this gene polymorphism was significantly associated with essential hypertension in women, suggesting the sexual dimorphism in genetic effect (P (<) 0.05). Further studied suggest that a larger sample size of this study are needed.

Leptin Polymorphisms Associated with Carcass Traits of Meat in Korean Cattle

  • Cheong, Hyun Sub;Yoon, Du-Hak;Kim, Lyoung Hyo;Park, Byung Lae;Chung, Eui Ryong;Lee, Han Ju;Cheong, Il-Cheong;Oh, Sung-Jong;Shin, Hyoung Doo
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.11
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    • pp.1529-1535
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    • 2006
  • Leptin has been investigated as a candidate gene for fat characteristics in beef cattle. Previously, we have reported 57 sequence variants discovered in Korean cattle (Bos Taurus coreanae). In this study, we examined the association between polymorphisms of leptin and carcass traits (cold carcass weight (CWT) and marbling score (Marb)) in Korean cattle. Among 57 polymorphisms, 11 common polymorphic sites were genotyped in our beef cattle (n = 437). Statistical analysis revealed that one single nucleotide polymorphism in coding exon (c.+411T>C (A137A)) showed a significant association with the yield trait, CWT. The C-bearing genotypes (CC or CT) of c.+411T>C (A137A) showed the higher CWT (p = 0.006). c.+150C>G (S50S) also showed a significant association with the quality trait, Marb (p = 0.01). Our findings suggest that polymorphisms in leptin might be one of the important genetic factors that influence carcass yield and quality in beef cattle, especially in CWT and Marb.