共查询到20条相似文献,搜索用时 31 毫秒
1.
L. R. Fraga C. G. Dutra J. A. Boquett F. S. L. Vianna R. O. Gonçalves D. D. Paskulin O. L. Costa P. Ashton-Prolla M. T. V. Sanseverino L. Schuler-Faccini 《Molecular biology reports》2014,41(3):1871-1877
The p53 protein is known for performing essential functions in the maintenance of genomic stability in somatic cells and prevention of tumor formation. Studies of the p53 signaling pathway have suggested associations between some polymorphisms and infertility, post-in vitro fertilization implantation failure and recurrent abortions. The TP53 Pro72Arg polymorphism has been implicated as a risk factor for recurrent pregnancy loss (RPL); however, the association is controversial. In this study, our objective was to evaluate selected polymorphisms in genes of the p53 signalling pathway [TP53 c.215G>C (Pro72Arg), MDM2 c.14+309T>G (SNP309) and LIF c.1414T>G in the region 3′ UTR] and determine their effect as risk factors for RPL. In a case–control study, we investigated 120 women with two or more pregnancy losses and 143 fertile control women reporting at least two live births and no history of pregnancy loss. When analyzed separately, the allele and genotype distributions of the polymorphisms in the two groups were not different. However, in a multivariate analysis adjusted for alcohol consumption, smoking, ethnicity, and number of pregnancies, the interaction between the genotypes TP53 Arg/Arg (rs1042522) and MDM2 TT (rs2279744) showed to be associated to RPL, increasing the risk for this condition (OR = 2.58, 95 % CI: 1.31–5.07, p = 0.006). In conclusion, our study indicates that the combination of TP53 Arg/Arg (rs1042522) and MDM2 TT (rs2279744) genotypes may be a risk factor for RPL. 相似文献
2.
Yu Weng Liqin Lu Guorong Yuan Jing Guo Zhizhong Zhang Xinyou Xie Guangdi Chen Jun Zhang 《PloS one》2012,7(9)
Background
Previous studies on the association of p53 codon 72 (Arg72Pro) polymorphism with hematological malignancies risk have produced conflicting results. The purpose of this meta-analysis is to define the effect of p53 Arg72Pro polymorphism on hematological malignancies risk.Methodology/Principal Findings
Through searching PubMed databases (or hand searching) up to April 2012 using the following MeSH terms and keywords: “p53”, “codon 72” “polymorphism” and “leukemia”, or “lymphoma”, or “myeloma”, thirteen were identified as eligible articles in this meta-analysis for p53 Arg72Pro polymorphism (2,731 cases and 7, 356 controls), including nine studies on leukemia (1,266 cases and 4, 474 controls), three studies on lymphoma (1,359 cases and 2,652 controls), and one study on myeloma. The overall results suggested that p53 Arg72Pro polymorphism was not associated with hematological malignancies risk. In stratified analyses, significantly increased non-Hodgkin lymphomas risk was found in p53 Arg72Pro polymorphism heterozygote model (Arg/Pro vs. Arg/Arg: OR = 1.18, 95%CI: 1.02–1.35) and dominant model (Arg/Pro+Pro/Pro vs. Arg/Arg: OR = 1.18, 95%CI: 1.03–1.34), but no significant association was found between leukemia risk and p53 Arg72Pro polymorphism. Further studies showed no association between leukemia risk and p53 Arg72Pro polymorphism when stratified in subtypes of leukemias, ethnicities and sources of controls.Conclusions/Significance
This meta-analysis indicates that the p53 Arg72Pro polymorphism may contribute to susceptibility to non-Hodgkin lymphomas. 相似文献3.
4.
Mohammed A. A. Alqumber Naseem Akhter Shafiul Haque Aditya K. Panda Raju K. Mandal 《PloS one》2014,9(4)
Aim
Allelic polymorphism in codon 72 of the p53 tumor suppressor gene causes imbalance of p53 protein expression. Earlier studies have shown association between allelic polymorphism in codon 72 of the p53 gene with risk of ovary cancer (OC); however the results are inconclusive and conflicting. Therefore, we performed this meta-analysis to investigate the relation between p53 codon 72 Arg>Pro polymorphism and overall OC susceptibility.Methods
We searched all eligible published studies based on the association between codon 72 of the p53 Arg>Pro polymorphism and risk of OC. Data were pooled together from individual studies and meta-analysis was performed. Pooled odds ratios (ORs) and 95% CI were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models.Results
A total of twelve studies comprising of 993 OC cases and 1264 healthy controls were included in this meta-analysis. Overall, no significant association was detected for Pro allele carrier (Pro vs. Arg: p = 0.916; OR = 0.980, 95% CI = 0.677 to 1.419), homozygous (Pro/Pro vs. Arg/Arg: p = 0.419; OR = 0.731, 95% CI = 0.341 to 1.564), heterozygous (Arg/Pro vs. Arg/Arg: p = 0.248; OR = 1.237, 95% CI = 0.862 to 1.773), dominant (Pro/Pro+Arg/Pro vsArg/Arg: p = 0.699; OR = 1.089, 95% CI = 0.706 to 1.681), and recessive (Pro/Pro vs Arg/Arg+Arg/Pro: p = 0.329; OR = 0.754, 95% CI = 0.428 to 1.329) genetic models, respectively. Also, in the stratified analysis by ethnicity, no significant association of this polymorphism with risk of OC was found in the Caucasian population.Conclusions
This meta-analysis suggested that codon 72 of the p53 Arg>Pro polymorphism may not significantly contribute in ovary cancer susceptibility. However, future large studies with gene-gene and gene-environment interactions are needed to validate these findings. 相似文献5.
Ezzikouri S Essaid El Feydi A Afifi R Benazzouz M Hassar M Pineau P Benjelloun S 《The International journal of biological markers》2011,26(4):229-233
Single-nucleotide polymorphisms (SNPs) in codon 72 of the TP53 gene (rs1042522) and in the promoter region of the MDM2 gene (SNP309; rs2279744) have been shown to play a role in the predisposition to many cancers. However, these findings were inconsistent in other tumor types, and ethnicity is suspected to be a critical factor influencing the effects of these SNPs on the cancer risk. The aim of the present study was to investigate whether these functional SNPs were associated with an enhanced risk of liver tumorigenesis in Moroccan patients. We have genotyped both polymorphisms in 96 patients with hepatocellular carcinoma (HCC) and 222 controls without HCC matched for age, gender and ethnicity by PCR-RFLP confirmed by sequencing. A joint effect between the MDM2 and TP53 polymorphisms and an increased risk of liver cancer was detected, with the odds ratio for the presence of both MDM2 309GG and TP53 72Pro/Pro genotypes being 10 (95% confidence interval 0.39-255.55). Interestingly, a significant increase in the HCC risk was observed when at least two deleterious alleles were present, indicating an allele dosage effect. There was no evidence for any association with early age of HCC onset when deleterious alleles of MDM2 SNP309 and TP53 Arg72Pro where present. Our findings suggest that the combination of TP53 72Pro and MDM2 309G polymorphisms enhance the risk of developing HCC. These results deserve further confirmation in other populations. 相似文献
6.
Ju Yang Bo Liu Wen Li Huihua Xiong Hong Qiu Qiang Fu Bei Chen Guangyuan Hu Xianglin Yuan 《Cancer epidemiology》2013,37(5):629-633
PurposeThough polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous tumors, particularly tumors associated with human papillomavirus (HPV) infection. However, the results remain controversial. Our previous study showed that HPV serostatus is not an independent risk factor for esophageal squamous cell carcinoma (ESCC) in nonsmokers and nondrinkers. Given the roles of p53 and HPV E6 as well as MDM2 oncoproteins in p53 degradation, we validated the association of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.MethodsSingle nucleotide polymorphisms of p53 Arg72Pro (rs1042522) and MDM2 (rs937283) in 307 ESCC patients and 311 healthy controls were genotyped. The presence or absence of HPV16 in serum was measured by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to evaluate the possible associations of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.ResultsPatients carrying p53 Arg/Arg or Arg/Pro had a higher risk of esophageal SCC (P < 0.001, Odds ratio [OR] 4.98, 95% confidential interval [CI] 3.46–7.17), however, not found in MDM2 rs937283. The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity (P < 0.001, OR 9.33, 95% CI 5.44–16.0), but not for MDM2 rs937283. The risk of esophageal SCC was further elevated among patients carrying Arg/Arg or Arg/Pro and HPV16-seropositivity who were smokers (P < 0.001, OR 27.05, 95% CI 11.06–66.16) or drinkers (P < 0.001, OR 13.20, 95% CI 5.74–30.38).ConclusionHPV16 seropositivity synergized with p53 Arg/Arg or Arg/Pro and increased ESCC risk, especially in smokers or drinkers. 相似文献
7.
Feng Gao Xiangyu Xiong Wenting Pan Xinyu Yang Changchun Zhou Qipeng Yuan Liqing Zhou Ming Yang 《PloS one》2015,10(8)
A functional rs4245739 A>C single nucleotide polymorphism (SNP) locating in the MDM43’-untranslated (3’-UTR) region creates a miR-191-5p or miR-887-3p targeting sites. This change results in decreased expression of oncogene MDM4. Therefore, we examined the association between this SNP and small cell lung cancer (SCLC) risk as well as its regulatory function in SCLC cells. Genotypes were determined in two independent case-control sets consisted of 520SCLC cases and 1040 controls from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The impact of the rs4245739 SNP on miR-191-5p/miR-887-3p mediated MDM4 expression regulation was investigated using luciferase reporter gene assays. We found that the MDM4 rs4245739AC and CC genotypes were significantly associated with decreased SCLC susceptibility compared with the AA genotype in both case-control sets (Shandong set: OR = 0.53, 95% CI = 0.32–0.89, P = 0.014; Jiangsu set: OR = 0.47, 95% CI = 0.26–0.879, P = 0.017). Stratified analyses indicated that there was a significantly multiplicative interaction between rs4245739 and smoking (P
interactioin = 0.048). After co-tranfection of miRNAs and different allelic-MDM4 reporter constructs into SCLC cells, we found that the both miR-191-5p and miR-887-3p can lead to significantly decreased MDM4 expression activities in the construct with C-allelic 3’-UTR but not A-allelic 3’-UTR, suggesting a consistent genotype-phenotype correlation. Our data illuminate that the MDM4rs4245739SNP contributes to SCLC risk and support the notion that gene 3’-UTR genetic variants, impacting miRNA-binding, might modify SCLC susceptibility. 相似文献
8.
Myung Su Son Moon Ju Jang Young Joo Jeon Won Hee Kim Chang-Il Kwon Kwang Hyun Ko Pil Won Park Sung Pyo Hong Kyu Sung Rim Sung Won Kwon Seong Gyu Hwang Nam Keun Kim 《Gene》2013
Background
Numerous studies have focused on the association between miR-34 family members, which are direct p53 targets, and carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). This study aimed to assess whether polymorphisms in the single-nucleotide polymorphism miR-34b/c T>C (rs4938723) and TP53 Arg72Pro (rs1042522) increase the risk of HCC and influence outcome in patients with HCC.Patients and methods
We enrolled 157 HCC patients and 201 cancer-free control subjects from the Korean population. MicroRNA polymorphisms were genotyped using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method.Results
We found that the miR-34b/c TC + CC frequency was significantly higher in HCC patients than in controls (adjusted odds ratio [AOR]: 1.580; 95% confidence interval [CI]: 1.029–2.426). The miR-34b/c CC-TP53 Arg/Arg combination significantly increased the risk of HCC (AOR: 13.644; 95% CI: 1.451–128.301). The SNPs miR-34b/c T>C and TP53 Arg72Pro(G>C) had no influence on survival of HCC patients.Conclusions
Our findings suggest that loss of the T allele in miR-34b/c T>C, and the miR-34b/c CC-TP53 Arg/Arg combination increases the risk of HCC in the Korean population. 相似文献9.
Raju S. R. Adduri Rajender Katamoni Ramaswamy Pandilla Sandeep N. Madana Arun Kumar Paripati Viswakalyan Kotapalli Murali Dharan Bashyam 《PloS one》2014,9(12)
Purpose
The tumor suppressor p53 is known to be inactivated frequently in various cancers. In addition, germline polymorphisms in TP53 are known to affect protein function and influence risk of developing different types of cancers. In this study, we analyzed the association of TP53 Pro72Arg polymorphism with squamous cell carcinoma of oral tongue (SCCOT) and esophagus (ESCC) in India.Methods
We assessed the distribution of TP53 Pro72Arg polymorphism in one hundred and fifteen and eighty two SCCOT and ESCC patients, respectively, with respect to one hundred and ten healthy controls from the same population. In addition, we analyzed association of the polymorphism with several clinico-pathological and molecular parameters.Results
Pro72 allele was significantly enriched in SCCOT patients compared to the healthy control group but neither allele was enriched in ESCC. Interestingly, Pro72 allele was preferentially mutated in ESCC which was confirmed by analysis of samples heterozygous for Pro72Arg.Conclusions
Our study revealed the association of Pro72 allele with SCCOT suggesting the effect of this polymorphism on SCCOT risk. Preferential mutation of Pro72 allele exclusively in ESCC indicates the need for further studies to understand the tissue specific effect of p53 polymorphism. 相似文献10.
Yasuki Hori Katsuyuki Miyabe Michihiro Yoshida Takahiro Nakazawa Kazuki Hayashi Itaru Naitoh Shuya Shimizu Hiromu Kondo Yuji Nishi Shuichiro Umemura Akihisa Kato Hirotaka Ohara Hiroshi Inagaki Takashi Joh 《PloS one》2015,10(3)
Single-nucleotide polymorphisms (SNPs) of TP53 (codon 72, rs1042522) and MDM2 promoter (SNP 309, rs2279744) have been associated with risk for various human cancers. However, studies analyzing these polymorphisms in pancreatic ductal adenocarcinoma (PDAC) are lacking. We investigated TP53 codon 72 and MDM2 SNP 309 polymorphisms in 32 patients with PDAC, 16 patients with chronic pancreatitis (CP), and 32 normal controls, using formalin-fixed paraffin-embedded tissue. We also examined TP53 and MDM2 protein immunohistochemistry (IHC) to assess the involvement of these differences in malignant transformation and disease progression. TP53 Pro/Pro genotype was significantly more frequent in PDAC patients than in controls (65.6 vs. 15.6%, p < 0.001) and no significant difference was found between CP patients (37.5%) and controls. In MDM2 SNP 309, there were no significant differences among the three groups. Based on the Kaplan-Meier analysis, overall survival was significantly shorter in MDM2 G/G genotypes compared with other genotypes (G/T and T/T) (359 vs. 911 days, p = 0.016) whereas no significant differences in TP53 genotypes were observed (638 vs. 752 days, p = 0.471). Although TP53 IHC was frequent in PDAC patients (53.1%), TP53 and MDM2 protein expression was not correlated with polymorphisms. Our study demonstrated TP53 codon 72 polymorphism is potentially a genetic predisposing factor while MDM2 SNP 309 polymorphism might be useful in predicting survival outcome. 相似文献
11.
Jamal S.M. Sabir Abdelfatteh El Omri Noor A. Shaik Babajan Banaganapalli Nahid H. Hajrah Houda Zrelli Leila Arfaoui Zuhier A. Awan Abdulkader M. Shaikh Omar Arif Mohammed Mona G. Alharbi Alawiah M. Alhebshi Robert K. Jansen Muhummadh Khan 《Saudi Journal of Biological Sciences》2019,26(7):1338-1343
Obesity is a multifactorial metabolic disorder characterized by low grade chronic inflammation. Rare and novel mutations in genes which are vital in several key pathways have been reported to alter the energy expenditure which regulates body weight. The TP53 or p53 gene plays a prominent role in regulating various metabolic activities such as glycolysis, lipolysis, and glycogen synthesis. Recent genome-wide association studies reported that tumor suppressor gene p53 variants play a critical role in the predisposition of type 2 diabetes and obesity. Till date, no reports are available from the Arabian population; hence the present study was intended to assess the association between p53 variants with risk of obesity development in the Saudi population. We have selected three p53 polymorphisms, rs1642785 (C > G), and rs9894946 (A > G), and rs1042522 (Pro72Arg; C > G) and assessed their association with obesity risk in the Saudi population. Phenotypic and biochemical parameters were also evaluated to check their association with p53 genotypes and obesity. Genotyping was carried out on 136 obese and 122 normal samples. We observed that there is significantly increased prevalence p52 Pro72Arg (rs1042522) polymorphism in obese persons when compared to controls at GG genotype in overall comparison (OR: 2.169, 95% CI: 1.086-4.334, p = 0.02716). Male obese subjects showed three-fold higher risk at GG genotype (OR: 3.275, 95% CI: 1.230-8.716, p = 0.01560) and two-fold risk at G allele (OR: 1.827, 95% CI: 1.128-2.958, p = 0.01388) of p53 variant Pro72Arg respectively. This variant has also shown significant influence on cholesterol, LDL level, and random insulin levels in obese subjects (p ≤ 0.05). In conclusion, p53 Pro72Arg variant is highly prevalent among obese individuals and may act as a genetic modifier for obesity development among Saudis. 相似文献
12.
Zhang Y Liu L Tang Y Chen C Wang Q Xu J Yang C Miao X Wei S Chen J Nie S 《Molecular biology reports》2012,39(10):9661-9668
The murine double minute 2 protein (MDM2) and TP53 interact in regulating cell cycle, DNA repair and apoptosis process, which is crucial in carcinogenesis. Since functional variations in these two genes were shown to change gene expression and function, we hypothesized that potentially functional polymorphisms in these genes may contribute to colorectal cancer (CRC) susceptibility. A hospital-based case-control study consisting of 444 patients and 569 controls was conducted to explore the associations between TP53 Arg72Pro and MDM2 T309G and CRC risk in Chinese. The combined effect of TP53 Arg72Pro and MDM2 T309G was significant in a gene dose-response increasing CRC risk (trend test: P?=?0.02). Individuals carrying 3 or more potential risk alleles had 1.78 times risk (95?% CI: 1.13-2.80) to develop CRC compared with individuals without potential risk allele. This increased cancer risk was more pronounced in smokers who carried 3-4 potential risk alleles (OR?=?2.75, 95?% CI: 1.14-6.60) and in young subjects (OR?=?2.05, 95?% CI: 1.08-3.88). The gene-gene interaction between TP53 Arg72Pro and MDM2 T309G may interact in carcinogenesis of CRC in Chinese, especially in smokers, and this kind of interaction is associated with onset age of CRC. 相似文献
13.
Background
TP53 gene is one of the most important tumor suppressor genes. We undertook this meta-analysis to explore the association between TP53 Arg72Pro polymorphism and the risk of skin cancer mainly in Caucasians.Methods
We searched PubMed for case-control studies published up to March 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.Results
A total of 5276 skin cancer cases and 5315 controls from 20 studies were included. Overall, no significant association between TP53 Arg72Pro polymorphism and skin cancer was observed in all genetic contrast models (Pro/Pro versus Arg/Arg, Pro/Arg versus Arg/Arg, Pro/Pro + Pro/Arg versus Arg/Arg, Pro/Pro versus Arg/Arg + Pro/Arg, Pro allele versus Arg allele). Similar results were obtained in the stratified analysis by ethnicity and histological types of skin cancer, such as melanoma, squamous cell carcinoma and basal cell carcinoma. Power calculations indicated that some studies were underpowered. No publication bias was found by using the funnel plot and Egger''s test.Conclusions
This meta-analysis indicated that TP53 Arg72Pro polymorphism probably had little association with skin cancer susceptibility mainly in Caucasians. However, larger sample-size studies are required to verify the conclusion as low statistical powers. 相似文献14.
V. I. Loginov M. V. Atkarskaya A. M. Burdennyy T. M. Zavarykina T. P. Kazubskaya V. V. Nosikov E. A. Braga G. P. Zhizhina 《Molecular Biology》2014,48(1):52-57
Association of TP53 Arg72Pro and MDM2 T309G polymorphic markers with the risk of non-small-cell lung cancer was studied in a Russian population of the Moscow region. The minor Pro/Pro genotype of Arg72Pro and the TG genotype of T309G were associated with non-small-cell lung cancer (OR = 5.46, p = 8 × 10?6 and OR = 7.38, p = 0.0001, respectively). Both Pro/Pro and TG genotypes were also strongly associated with lung adenocarcinoma (OR = 8.71, p = 3 × 10?6 and OR = 8.13, p = 0.003, respectively) and squamous-cell lung carcinoma (OR = 4.2, p = 0.001 and OR = 7.02, p = 0.002, respectively). Finally, combined susceptible genotypes of TP53 and MDM2 polymorphisms Arg72Pro and T309G were reliably associated with non-small-cell lung cancer and both its subtypes (OR = 7.9, p = 0.01; OR = 9.12, p = 0.02; OR = 7.31, p = 0.03, respectively). 相似文献
15.
Krzysztof Mędrek Piotr Magnowski Bartłomiej Masojć Anita Chudecka-Głaz Bogdan Torbe Janusz Menkiszak Marek Spaczyński Jacek Gronwald Jan Lubiński Bohdan Górski 《Molecular biology reports》2013,40(3):2145-2147
Among many alterations within the TP53 gene the rs1042522 (C72G, p.Pro72Arg) has been associated with numerous cancers , however the results differ between populations for opposite Pro or Arg alleles. Similar thus inconclusive results are observed in ovarian cancer, which may suggest that the rs1042522 does not influence ovarian carcinogensis directly, but might be linked to another pathogenic alteration. WRAP53 which overlaps the TP53 is required to maintain normal levels of p53 upon DNA damage, but also when altered may independently increase the risk of cancer. To evaluate the association between three SNPs located in WRAP53–TP53 region: rs1042522, rs2287497, rs2287498 and ovarian cancer risk in Polish population we genotyped 626 cases and 1,045 healthy controls. Our results provide the evidence for an association between studied SNPs and a risk of invasive ovarian cancer in Poland. We found that CC homozygotes in rs1042522 were more frequent in cancers when compared to controls (OR = 1.46, p = 0.03). Similarly in WRAP53 both TT homozygotes in rs2287497 (OR = 1.95, p = 0.03) and AA homozygotes in rs2287498 (OR = 2.65, p = 0,01) were more frequent among cases than healthy individuals. There is also a suggestive evidence that specific homozygosity of studied SNPs in TP53–WRAP53 region is significantly overrepresented in ovarian cancer patients. In conclusion SNPs in WRAP53 (rs2287497 and rs2287498) have stronger association with an ovarian cancer risk than rs1042522 in TP53. 相似文献
16.
Previous studies investigating the association between TP53 Arg72Pro polymorphism and bladder cancer risk reported controversial results. To quantify the strength of association between TP53 Arg72Pro polymorphism and bladder cancer risk, we performed this meta-analysis. We searched PubMed, Embase and Wangfang databases for studies relating the association between TP53 Arg72Pro polymorphism and bladder cancer risk. We used the pooled odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) to assess the association. Finally, data were available from a total of 16 case–control studies including a total of 5, 545 subjects (2,345 cases and 3,200 controls). Meta-analysis of all 16 studies showed TP53 Arg72Pro polymorphism was not associated with bladder cancer risk (All P values were more than 0.10). Subgroup analyses by ethnicity showed that TP53 Arg72Pro polymorphism contributed to bladder cancer risk in East Asians in three genetic models (For Pro vs. Arg, Fixed-effects OR 1.18, 95 % CI 1.05–1.32; For ProPro vs. ArgArg, Fixed-effects OR 1.40, 95 % CI 1.11–1.77; For ProPro vs. ArgPro/ArgArg, Fixed-effects OR 1.32, 95 % CI 1.07–1.62). However, there was no significant association in Caucasians and the others (All P values were more than 0.05). Heterogeneity analyses suggested ethnicity was the major sources of heterogeneity. Thus, meta-analyses of available data suggest the Pro variant of TP53 Arg72Pro contributes to bladder cancer risk in East Asians. Besides, TP53 Arg72Pro polymorphism may have race-specific effects on bladder cancer risk and further studies are needed to elucidate this possible effect. 相似文献
17.
To evaluate the associations between candidate FTO single nucleotide polymorphisms (SNPs) and obesity, a case-control study was conducted among Chinese school-age children, which included 500 obese cases and 500 matched controls (age, gender and location). We selected 24 candidate FTO tag-SNPs via bio-informatics analysis and performed genotyping using SNPScan technology. Results indicated that rs7206790 and rs11644943 were significantly associated with obesity among school-age children in both additive and recessive models (P<0.05) after adjusting confounders. Comparing rs7206790 CC and CG genotype of carriers, those carrying the GG genotype had an increased risk of obesity (adjusted odds ratio [OR], 3.76; 95% Confidence interval [CI], 1.24–11.43). Carriers of the AA allele of rs11644943 had a lower risk of obesity (adjusted OR, 0.16; 95% CI, 0.04–0.72) compared with those of the T allele (TT and TA). These two SNPs (rs7206790 and rs11644943) were not Linkage Disequilibrium (LD) with previous reported obesity-associated SNPs. Under the recessive model adjusted for age and gender and location, rs7206790 GG allele carriers had significantly increased BMIs (P = 0.012), weight (P = 0.012), waist circumferences (WC) (P = 0.045) and hip circumferences (HC) (P = 0.033). Conversely, rs11644943 AA allele carriers had significantly decreased BMIs (P = 0.006), WC (P = 0.037) and Waist-to-height ratios (WHtR) (P = 0.012). A dose-response relationship was found between the number of risk alleles in rs7206790, rs11644943 and rs9939609 and the risk of obesity. The Genetic Risk Score (GRS) of the reference group was 3; in comparison, those of 2, 4, and ≥5 had ORs for obesity of 0.24 (95%CI, 0.05–1.13), 1.49 (95%CI, 1.10–2.01), and 5.20 (95%CI, 1.75–15.44), respectively. This study confirmed the role of FTO variation on genetic susceptibility to obesity. We reported two new obesity-related FTO SNPs (rs7206790 and rs11644943) among Chinese school-age children. 相似文献
18.
Growing bodies of studies have been conducted on the association of TP53 Arg72Pro polymorphism with susceptibility to ovarian cancer and have yielded conflicting results. Thus, a meta-analysis was
performed to summarize the possible association. 18 case–control studies, including 2,193 ovarian cancer cases and 5,175 controls
were identified. The quality of the studies was assessed according to a predefined scale. The strength of the associations
between TP53 Arg72Pro polymorphism and ovarian cancer was measured by crude odds ratios (ORs) with 95% confidence intervals (CIs). Overall,
no significant association was found between TP53 Arg72Pro polymorphism and ovarian cancer risk when all studies pooled into the meta-analysis in all genetic model. In the
subgroup analysis by ethnicity, still no association of this polymorphism with ovarian cancer risk was obtained for all comparison
models. However, significantly decreased risks of ovarian cancer were found for Arg/Arg versus Arg/Pro+Pro/Pro (OR 0.84, 95%
CI 0.74–0.96) when the analysis was restricted to high quality studies. Conversely, when it was restricted to low quality
studies, significantly increased risks were observed for Arg/Arg versus Pro/Pro (OR 1.58, 95% CI 1.09–2.28) and Arg/Arg+Arg/Pro
versus Pro/Pro: (OR 1.50, 95% CI 1.10–2.06), which might be spurious due to the poor design of these studies. In conclusion,
this meta-analysis suggests that the Arg allele is at a moderately reduced risk for ovarian cancer and this polymorphism might
protect against ovarian carcinogenesis. 相似文献
19.
Janey L. Wiggs Alex W. Hewitt Bao Jian Fan Dan Yi Wang Dayse R. Figueiredo Sena Colm O’Brien Anthony Realini Jamie E. Craig David P. Dimasi David A. Mackey Jonathan L. Haines Louis R. Pasquale 《PloS one》2012,7(9)
Background
Loss of vision in glaucoma is due to apoptotic retinal ganglion cell loss. While p53 modulates apoptosis, gene association studies between p53 variants and glaucoma have been inconsistent. In this study we evaluate the association between a p53 variant functionally known to influence apoptosis (codon 72 Pro/Arg) and the subset of primary open angle glaucoma (POAG) patients with early loss of central visual field.Methods
Genotypes for the p53 codon 72 polymorphism (Pro/Arg) were obtained for 264 POAG patients and 400 controls from the U.S. and in replication studies for 308 POAG patients and 178 controls from Australia (GIST). The glaucoma patients were divided into two groups according to location of initial visual field defect (either paracentral or peripheral). All cases and controls were Caucasian with European ancestry.Results
The p53-PRO/PRO genotype was more frequent in the U.S. POAG patients with early visual field defects in the paracentral regions compared with those in the peripheral regions or control group (p = 2.7×10−5). We replicated this finding in the GIST cohort (p = 7.3×10−3, and in the pooled sample (p = 6.6×10−7) and in a meta-analysis of both the US and GIST datasets (1.3×10−6, OR 2.17 (1.58–2.98 for the PRO allele).Conclusions
These results suggest that the p53 codon 72 PRO/PRO genotype is potentially associated with early paracentral visual field defects in primary open-angle glaucoma patients. 相似文献20.