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Yinchen Shen Zujia Wen Ning Wang Zhi Zheng Kun Liu Xin Xia Qing Gu Yongyong Shi Xun Xu 《PloS one》2014,9(11)
Purpose
The aim of this study was to investigate variants in UCP2 genes in type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) in Chinese population.Materials and Methods
We conducted a single nucleotide polymorphism-based and haplotype-based case-control study between the variants of UCP2 and DM and between the variants of UCP2 and DR in 479 Chinese patients with type 2 DM and 479 control subjects without DM. Two SNPs (rs660339 and rs659366) were selected as genetic markers.Results
The risk allele C at UCP2 rs660339 was closely associated with DM in Chinese population. There was significant difference in rs660339 between DM and controls (P = 0.0016; OR [95%CI] = 1.37 (1.14–1.65)). Subjects who were homozygous of the C allele were more likely to develop DM. The frequency of C allele was higher in DM (58%) than in control (51%). But this locus didn''t have a definite effect on the onset of non-proliferative diabetic retinopathy (NPDR) (P = 0.44; OR [95%CI] = 0.80 (0.56–1.14)) and proliferative diabetic retinopathy (PDR) (P = 1.00; OR [95%CI] = 0.99 (0.74–1.34)) comparing to subjects with DM without retinopathy (DWR), respectively. Moreover, the UCP2 rs659366 polymorphism showed no significant difference between DM and control (P = 0.66; OR [95%CI] = 1.10 (0.91–1.32)). However, there was a significant difference between PDR and DWR (P = 0.016; OR [95%CI] = 0.66 (0.49–0.90)), but there was no difference between NPDR and DWR (P = 1.00; OR [95%CI] = 0.96 (0.67–1.37)). Participants who carried the G allele at rs659366 were more likely to develop PDR. For the haplotype, C-A was present more frequently in DM than in control (16% vs 7%), indicating that it was risky, and T-A was present less in DM than in control (29% vs 35%). Haplotype frequencies in DR and DWR showed no significant difference (P = 0.068).Conclusion
It was indicated that UCP2 may be implicated in the pathogenesis of type 2 DM and DR in Chinese population. 相似文献3.
Ana P. Bou?as Letícia A. Brondani Bianca M. Souza Natália E. Lemos Fernanda S. de Oliveira Luis H. Canani Daisy Crispim 《PloS one》2013,8(12)
Background
The rs1990760 polymorphism of interferon induced with helicase C domain 1 (IFIH1) has been associated with type 1 diabetes mellitus (T1DM). Here, we investigated whether this polymorphism is associated with T1DM or its clinical characteristics in a Brazilian population, and if IFIH1 gene expression in mononuclear cells from T1DM patients differs according to the genotypes of this polymorphism. A meta-analysis was also conducted to evaluate if the rs1990760 polymorphism is associated with T1DM.Methods
Frequencies of the rs1990760 polymorphism were analyzed in 527 T1DM patients and in 517 healthy subjects. IFIH1 gene expressions according to genotypes were measured in a sub-sample of 26 T1DM patients by quantitative real-time PCR.Results
Our data show the association of the A allele with risk to T1DM under a dominant model of inheritance [odds ratio (OR) = 1.421, P = 0.037], adjusting for ethnicity. The meta-analysis revealed significant association between the rs199760A allele and risk for T1DM for all analyzed inheritance models. Surprisingly, T1DM patients carrying the A allele showed lower levels of systolic (P = 0.001) and diastolic (P = 1×10−10) blood pressures as compared to G/G carriers. Furthermore, the A/A genotype seems to be associated with protection to arterial hypertension (AH) after adjustment for covariates (OR = 0.339, P = 0.019). IFIH1 gene expression in mononuclear cells from 26 T1DM patients did not differ among genotypes (P = 0.274). Nevertheless, IFIH1 gene expression was increased in mononuclear cells from T1DM patients with AH as compared with T1DM patients without AH [6.7 (1.7–2.0) vs. 1.8 (1.3–7.1) arbitrary units; P = 0.036]. The association with blood pressures and AH was not observed in patients with type 2 diabetes mellitus.Conclusions
Our results indicate that the rs1990760 polymorphism is associated with T1DM. Interestingly, the rs1990760 A allele seems to be associated with protection for AH in T1DM patients. Further studies are needed to confirm the association with AH. 相似文献4.
Background and Objectives
Based on the results of previous studies, the ADD3 gene, located in the 10q24.2 region, may be a susceptibility gene of biliary atresia (BA). In this study, two single nucleotide polymorphisms (SNPs) in the ADD3 gene, rs17095355 C/T and rs10509906 G/C, were selected to investigate whether there is an association between these SNPs and susceptibility to BA in a Chinese population.Methods
A total of 752 Han Chinese (134 BA cases and 618 ethnically matched healthy controls) were included in the present study. The ADD3 gene polymorphisms were genotyped using a TaqMan genotyping assay.Results
Positive associations were found for the SNP rs17095355 in the codominant model; specifically, the frequencies of the CT and TT genotypes and the T allele were higher in the cases than the controls, demonstrating a significant risk for BA (odds ratio [OR] = 1.62, 95% confidence interval [CI] = 1.02–2.58; OR = 2.89, 95% CI = 1.72–4.86; and OR = 1.75, 95% CI = 1.34–2.29, respectively). Regarding rs10509906, the per-C-allele conferred an OR of 0.70 (95% CI = 0.49–1.00) under the additive model. A greater risk of BA was associated with the Ta-Gb (a for rs17095355 and b for rs10509906) haplotype (OR = 1.82, 95% CI = 1.27–2.61) compared with the Ca-Cb haplotype.Conclusion
This study suggests that the ADD3 gene plays an important role in BA pathogenesis and reveals a significant association between two SNPs, rs17095355 and rs10509906, and BA. 相似文献5.
Yan-yan Li Zhi-jian Yang Chuan-wei Zhou Xiang-ming Wang Yun Qian Jian Xu Bei Wang Jun Wu 《PloS one》2013,8(4)
Background
Although adiponectin −11377CG gene polymorphism is implied to be associated with increased type 2 diabetes mellitus (T2DM) risk, results of individual studies are inconsistent.Objective and Methods
A meta-analysis consisting of 12 individual studies, including a total of 6425 participants, was carried out in order to investigate the association of adiponectin −11377CG gene polymorphism with T2DM. The pooled odds ratio (OR) and its corresponding confidence interval (CI) at 95% were assessed through the random- or fixed- effect model.Results
A significant relationship was observed between adiponectin −11377CG gene polymorphism and T2DM under allelic (OR: 1.150, 95% CI: 1.060 to 1.250, P = 0.001), recessive (OR: 1.450, 95% CI: 1.180–1.770, P = 0.0004), dominant (OR: 1.071, 95% CI: 1.013–1.131, P = 0.015), additive (OR: 1.280, 95% CI: 1.090–1.510, P = 0.002), and homozygous genetic models (OR: 1.620, 95% CI: 1.310–1.990, P<0.00001). No significant association was found between them under the heterozygous genetic model (OR: 1.640, 95% CI: 0.850–3.170, P = 0.140).Conclusions
Adiponectin −11377CG gene polymorphism was significantly associated with T2DM risk susceptibility. G allele carriers are predisposed to T2DM risk. 相似文献6.
Fotios Loupakis Chiara Cremolini Dongyun Yang Lisa Salvatore Wu Zhang Takeru Wakatsuki Pierre Bohanes Marta Schirripa Leonor Benhaim Sara Lonardi Carlotta Antoniotti Giuseppe Aprile Francesco Graziano Annamaria Ruzzo Sara Lucchesi Monica Ronzoni Ferdinando De Vita Giuseppe Tonini Alfredo Falcone Heinz-Josef Lenz 《PloS one》2013,8(7)
Purpose
The potential impact of different SNPs of VEGF/VEGFR pathway on the clinical outcome of mCRC patients receiving bev-containing regimens has been investigated in retrospective experiences with contrasting results. We previously reported the association of VEGFA rs833061 C/T variants with PFS in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab. The primary objective of this work was to prospectively validate that retrospective finding. A confirmatory analysis of other SNPs of VEGF/VEGFR pathway genes was included.Experimental design
To detect a HR for PFS of 1.7 for VEGFA rs833061 T/T compared to C- variants in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab, setting two-sided α = 0.05 and β = 0.20, 199 events were required. VEGFA rs699946 A/G, rs699947 A/C, VEGFR1 rs9582036 A/C and rs7993418 A/G, VEGFR2 rs11133360 C/T, rs12505758 C/T and rs2305948 C/T and EPAS1 rs4145836 A/G were also tested. Germ-line DNA was extracted from peripheral blood. SNPs were analyzed by PCR and sequencing.Results
Four-hundred-twenty-four pts were included. At the univariate analysis, no differences according to VEGFA rs833061 C/T variants were observed in PFS (p = 0.38) or OS (p = 0.95). Among analyzed SNPs, only VEGFR2 rs12505758 C- variants, compared to T/T, were associated to shorter PFS (HR: 1.36 [1.05–1.75], p = 0.015, dominant genetic model) and OS, with a trend toward significance (HR: 1.34 [0.95–1.88], p = 0.088). In the multivariate model, this association retained significance (HR: 1.405 [1.082–1.825], p = 0.012) in PFS, that was lost by applying multiple testing correction (p = 0.14).Conclusion
This prospective experience failed to validate the hypothesized predictive impact of VEGFA rs833061 variants. Retrospective findings on different candidate SNPs were not confirmed. Only VEGFR2 rs12505758 variants, whose prognostic and not predictive impact was previously reported, correlated with PFS. Given the complexity of angiogenesis, it is rather unlike that a single germ-line SNP might be a good predictor of benefit from bevacizumab. 相似文献7.
Yifang Han Rui Pu Xue Han Jun Zhao Yuwei Zhang Qi Zhang Jianhua Yin Jiaxin Xie Qiuxia Shen Yang Deng Yibo Ding Weiping Li Juhong Li Hongwei Zhang Guangwen Cao 《PloS one》2013,8(3)
Background
Genetic polymorphisms of pri-miR-34b/c and pre-miR-196a2 have been reported to be associated with the susceptibility to cancers. However, the effect of these polymorphisms and their interactions with hepatitis B virus (HBV) mutations on the development of hepatocellular carcinoma (HCC) remains largely unknown. We hypothesized that these polymorphisms might interact with the HBV mutations and play a role in hepatocarcinogenesis.Methods
Pri-miR-34b/c rs4938723 (T>C) and pre-miR-196a2 rs11614913 (T>C) were genotyped in 3,325 subjects including 1,021 HBV-HCC patients using quantitative PCR. HBV mutations were determined by direct sequencing. Contributions of the polymorphisms and their multiplicative interactions with gender or HCC-related HBV mutations to HCC risk were assessed using multivariate regression analyses.Results
rs4938723 CC genotype was significantly associated with HCC risk compared to HBV natural clearance subjects, adjusted for age and gender (adjusted odds ratio [AOR] = 2.01, 95% confidence interval [CI] = 1.16–3.49). rs4938723 variant genotypes in dominant model significantly increased HCC risk in women, compared to female healthy controls (AOR = 1.85, 95% CI = 1.20–2.84) or female HCC-free subjects (AOR = 1.62, 95% CI = 1.14–2.31). rs4938723 CC genotype and rs11614913 TC genotype were significantly associated with increased frequencies of the HCC-related HBV mutations T1674C/G and G1896A, respectively. rs11614913 was not significantly associated with HCC risk, but its CC genotype significantly enhanced the effect of rs4938723 in women. In multivariate regression analyses, rs4938723 in dominant model increased HCC risk (AOR = 1.62, 95% CI = 1.05–2.49), whereas its multiplicative interaction with C1730G, a HBV mutation inversely associated with HCC risk, reduced HCC risk (AOR = 0.34, 95% CI = 0.15–0.81); rs11614913 strengthened the G1896A effect but attenuated the A3120G/T effect on HCC risk.Conclusions
rs4938723 might be a genetic risk factor of HCC but its effect on HCC is significantly affected by the HBV mutations. rs11614913 might not be a HCC susceptible factor but it might affect the effects of the HBV mutations or rs4938723 on HCC risk. 相似文献8.
Sayeh Ezzikouri Rhimou Alaoui Khadija Rebbani Ikram Brahim Fatima-Zohra Fakhir Salwa Nadir Helmut Diepolder Salim I. Khakoo Mark Thursz Soumaya Benjelloun 《PloS one》2013,8(1)
Background
Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population.Methods
We analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5′ allelic discrimination assay.Results
The protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99–11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19–66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99–3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08–8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40–3.93; p = 0.0100).Conclusions
In the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection. 相似文献9.
Xiaowei Wei Xiaowei Ma Ran Lu Ge Bai Jianwei Zhang Ruifen Deng Nan Gu Nan Feng Xiaohui Guo 《PloS one》2014,9(1)
Background
Insulin and glucagon-like peptide 1 (GLP-1), converted by proprotein convertase 1 (PC1/3) from proinsulin and proglucagon, are associated with type 2 diabetes (T2DM) and coronary artery disease (CAD). The aim of this study is to investigate the association of PCSK1 gene, which encodes PC1/3, with the risk of CAD in Chinese patients with T2DM.Methods
We selected and genotyped 5 haplotype-tagging single nucleotide polymorphisms (SNPs) at PCSK1 gene (across 39873bp locus) in a case-control study of Chinese Han population involving 425 diabetic patients (62.1% male, mean age 63.2 years) with CAD as positive cases and 258 diabetic patients (44.2% male, mean age 62.0 years) without CAD as controls.Results
The allele frequencies at rs3811951 were significantly different between cases and controls (30.7% vs. 37.2%), with the allele G associated with decreased risk for CAD (OR = 0.75, 95% CI = 0.59–0.94, p = 0.013). In recessive inheritance mode, the carriers of GG had a lower risk (OR = 0.50, 95%CI = 0.31–0.82, p = 0.005), even after adjusted for gender, age, BMI and smoking (OR = 0.43, 95%CI = 0.24–0.77, p = 0.004). The carriers of the minor allele A at rs156019 had a higher risk (OR = 1.66, 95%CI = 1.10–2.50, p = 0.016 after adjustment) in dominant inheritance mode. The SNP rs6234 was also significantly associated with CAD risk in women, with the carriers of the minor allele G at rs6234 associated with a reduced CAD risk in recessive inheritance mode (OR = 0.42, 95% CI = 0.18–0.95, p = 0.036 after adjustment).Conclusions
Our results found that common genetic variants in PCSK1 were associated with CAD in Chinese patients with T2DM. 相似文献10.
Jiayu Duan Jiao Lou Qing Zhang Juntao Ke Yanqi Qi Na Shen Beibei Zhu Rong Zhong Zhenling Wang Lifeng Liu Jing Wu Wei Wang Fangqi Gong Xiaoping Miao 《PloS one》2014,9(8)
Objectives
Recent genome-wide association study found rs1801274, a functional single nucleotide polymorphism (SNP) in IgG receptor gene FCGR2A, was associated with increased risk of Kawasaki disease (KD). However, subsequent studies on the role of this SNP were limited and controversial.Methods
A case-control study was conducted in a Chinese Han population including 428 KD patients and 493 controls to examine the association between rs1801274 and KD susceptibility. A meta-analysis was performed in combination with the relevant published studies to further clarify such an association.Results
Our case-control study found that rs1801274 was significantly associated with increased risk of KD in the Chinese Han population, with an odds ratio (OR) of 1.58 (95% CI = 0.96–2.62) for the GA genotype and 1.93 (95% CI = 1.16–3.19) for the AA genotype compared with the GG genotype. The result of meta-analysis further demonstrated that the A allele of rs1801274 was significantly correlated with KD risk under the allelic model (OR = 1.35, 95% CI = 1.27–1.44) without heterogeneity by fixed-effects model analysis (Q = 17.30, p = 0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis.Conclusion
These results further confirm that rs1801274 in the FCGR2A gene is significantly associated with increased risk of KD. 相似文献11.
Camilla Noelle Rathcke Johan Holmkvist Torben J?rgensen Knut Borch-Johnsen Torben Hansen Oluf Borbye Pedersen Henrik Vestergaard 《PloS one》2009,4(5)
Background
CHI3LI encoding the inflammatory glycoprotein YKL-40 is located on chromosome 1q32.1. YKL-40 is involved in inflammatory processes and patients with Type 2 Diabetes (T2D) have elevated circulating YKL-40 levels which correlate with their level of insulin resistance. Interestingly, it has been reported that rs10399931 (−329 G/A) of CHI3LI contributes to the inter-individual plasma YKL-40 levels in patients with sarcoidosis, and that rs4950928 (−131 C/G) is a susceptibility polymorphism for asthma and a decline in lung function. We hypothesized that single nucleotide polymorphisms (SNPs) or haplotypes thereof the CHI3LI locus might influence risk of T2D. The aim of the present study was to investigate the putative association between SNPs and haplotype blocks of CHI3LI and T2D and T2D related quantitative traits.Methods/Principal Findings
Eleven SNPs of CHI3LI were genotyped in 6514 individuals from the Inter99 cohort and 2924 individuals from the outpatient clinic at Steno Diabetes Center. In cas-control studies a total of 2345 T2D patients and 5302 individuals with a normal glucose tolerance test were examined.We found no association between rs10399931 (OR, 0.98 (CI, 0.88–1.10), p = 0.76), rs4950928 (0.98 (0.87–1.10), p = 0.68) or any of the other SNPs with T2D. Similarly, we found no significant association between any of the 11 tgSNPs and T2D related quantitative traits, all p>0.14. None of the identified haplotype blocks of CHI3LI showed any association with T2D, all p>0.16.Conclusions/Significance
None of the examined SNPs or haplotype blocks of CHI3LI showed any association with T2D or T2D related quantitative traits. Estimates of insulin resistance and dysregulated glucose homeostasis in T2D do not seem to be accounted for by the examined variations of CHI3LI. 相似文献12.
Nana Zhang Maoqiang Zhuang Aixia Ma Guochang Wang Ping Cheng Yajun Yang Xiaofeng Wang Juan Zhang Xingdong Chen Ming Lu 《PloS one》2013,8(12)
Objective
To investigate the association of Mannose-binding lectin (MBL) and the MBL2 gene with type 2 diabetes and diabetic nephropathy and the influence of MBL2 polymorphisms on serum MBL levels.Methods
The study population included 675 type 2 diabetic patients with or without nephropathy and 855 normoglycemic controls. The single nucleotide polymorphisms (SNPs) of rs1800450, rs1800451, and rs11003125 of the MBL2 gene were determined by the Multiplex Snapshot method. Serum MBL levels were measured by enzyme-linked immune sorbent assay.Results
Rs1800450 and rs11003125 SNPs demonstrated strong linkage disequilibrium in the study population (r2 = 0.97). The haplotypes constructed from the G allele of rs1800450 and the C allele of rs11003125 increased the risk for type 2 diabetes (OR = 1.2, 95% CI = 1.1–1.4, P = 0.01). For rs1800450, GG and GA genotypes were associated with type 2 diabetes (P = 0.02, 0.01, respectively). For rs11003125, the GC genotype frequency was significantly different between patients and controls (18.1% vs. 24.9%, P = 0.001). Analyses of genotypes and allele frequency distributions among patients with normal UAE, microalbuminuria, and macroalbuminuria showed that there was no obvious evidence of association between the MBL2 gene and diabetic nephropathy. Subjects with the GG genotype of rs1800450 and the CC genotype of rs11003125 had much higher serum MBL levels.Conclusions
The rs1800450 and rs11003125 SNPs of the MBL2 gene have strong linkage disequilibrium and are associated with type 2 diabetes in the North Chinese Han population. No association was observed between the MBL2 gene and diabetic nephropathy. Subjects with the GG genotype of rs1800450 and the CC genotype of rs11003125 had much higher serum MBL levels. An association between elevated serum MBL and diabetic nephropathy was also observed. 相似文献13.
Lingjun Zhu Mulong Du Dongying Gu Lan Ma Haiyan Chu Na Tong Jinfei Chen Zhengdong Zhang Meilin Wang 《PloS one》2013,8(3)
Background
A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population.Methods
We examined the associations between rs7758229 and colorectal cancer risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic regression model was used to assess the associations.Results
No significant association was found between rs7758229 and colorectal cancer risk (OR = 0.95, 95%CI = 0.84–1.09, P = 0.463). Similar results were observed in the stratification of tumor location (OR = 0.94, 95%CI = 0.80–1.11, P = 0.481 for colon cancer, and OR = 0.96, 95%CI = 0.82–1.13, P = 0.621 for rectum cancer).Conclusions
Our findings did not support an association between rs7758229 in 6q26-q27 and the risk of colorectal cancer in a Chinese population. 相似文献14.
Background
Several studies have been conducted in recent years to evaluate the risk of type 2 diabetes mellitus (T2DM) and polymorphisms of interleukin (IL)-10. However, the results remain conflicting rather than conclusive. This meta-analysis aimed to summarize the current evidence from case-control studies that evaluated this association.Methods
We carried out a search in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) database for relevant studies. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association.Results
10 studies were included in our meta-analysis and systemic review. Our meta-analysis indicated that IL-10 −1082A/G polymorphism was associated with the risk of T2DM (GA vs. AA: OR = 1.21, 95% CI = 1.03–1.14; GA/GG vs. AA: OR = 1.22, 95% CI = 1.05–1.41), whereas there was no association between IL-10 −592C/A (CC/CA vs. AA: OR = 1.07, 95% CI = 0.59–1.93) or -819C/T (CC/CT vs. TT: OR = 0.93, 95% CI = 0.49–1.75) polymorphism and T2DM risk was found in our study.Conclusions
This meta-analysis provides strong evidence that IL-10 −1082A/G polymorphism associated with risk of T2DM. However, no association of the IL-10 −592C/A or −819C/T polymorphism with T2DM risk was found. Additional well-designed large studies were required for the validation of our results. 相似文献15.
Background
Several studies have investigated whether the polymorphisms in the prostaglandin endoperoxide synthase 1 (PTGS1) and PTGS2 genes and nonsteroidal anti-inflammatory drug (NSAID) use are associated with cancer risk; however, those studies have produced mixed results. Therefore, we performed a meta-analysis to evaluate the association between the PTGS1 and PTGS2 polymorphisms and the effect of NSAID use on the risk of developing cancer.Methods
We conducted a comprehensive search in PubMed through March 2012. The odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated using the fixed-effect model or the random-effect model.Results
The database search generated 13 studies that met the inclusion criteria. For PTGS1 rs3842787, NSAID users homozygous for the major allele (CC) had a significantly decreased cancer risk compared with non-NSAID users (OR = 0.73, 95% CI = 0.59–0.89). For PTGS2 rs5275 and rs20417, there were no significant differences between the gene polymorphism and NSAID use on cancer risk among the 8 and 7 studies, respectively. However, in the stratified analysis by the type of cancer or ethnicity population, NSAID users homozygous for the major allele (TT) in rs5275 demonstrated significantly decreased cancer risk compared with non-NSAID users in cancer type not involving colorectal adenoma (OR = 0.70, 95% CI = 0.59–0.83) and among the USA population (OR = 0.67, 95% CI = 0.56–0.82). NSAID users homozygous for the major allele (GG) in rs20417 displayed a significantly decreased cancer risk than non-NSAID users among the US population (OR = 0.72, 95% CI = 0.58–0.88). For the PTGS2 rs689466 and rs2745557 SNPs, there were no significant differences.Conclusion
This meta-analysis suggests that the associations between PTGS polymorphisms and NSAID use on cancer risk may differ with regard to the type of cancer and nationality. 相似文献16.
Polymorphisms in Inflammasome Genes and Risk of Coal Workers' Pneumoconiosis in a Chinese Population
Xiaoming Ji Zhiguo Hou Ting Wang Kexin Jin Jingjing Fan Chen Luo Minjuan Chen Ruhui Han Chunhui Ni 《PloS one》2012,7(10)
Background
Coal workers'' pneumoconiosis (CWP), resulting from the inhalation of silica-containing coal mine dust, is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Recently, it has been hypothesized that inflammasomes could have a crucial role in the host response to silica and recent studies show that the inflammasome contributes to inflammation and pulmonary fibrosis. NLRP3, CARD8 are components of the NLRP3 inflammasome, which triggers caspase 1-mediated IL-1β and IL-18 release. In the present study, we investigated whether common single nucleotide polymorphisms (SNPs) in inflammasome genes are associated with CWP.Methods
We performed an association study analyzing 3 NLRP3, 1 CARD8, 1 IL-1β, 2 IL-18 SNPs in a case-control study of 697 CWP and 694 controls. Genotyping was carried out by the TaqMan method.Results
The NLRP3 rs1539019 TT genotype was associated with a significantly increased risk of CWP (adjusted odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.07–1.81), compared with the GG/GT genotype, in particular among smokers (adjusted OR = 1.67, 95%CI = 1.15–2.42). In addition, the polymorphism was significantly associated with risk of CWP patients with stage I.Conclusions
This is the first report showing an association between the NLRP3 rs1539019 polymorphism and CWP, and suggests that this polymorphism may confer increased risk for the development of the disease. Further studies are warranted to confirm our findings. 相似文献17.
Background
Preeclampsia, characterized by hypertension and proteinuria, is a multifactorial disease caused by complex interactions between environmental and genetic factors. A recent genome-wide association study of blood pressure reported an association between hypertension and rs11646213. This study evaluated the association between preeclampsia and rs11646213.Methods
A total of 454 cases and 460 controls were recruited to participate in this study. The single nucleotide polymorphism (SNP) rs11646213 was genotyped by polymerase chain reaction (PCR) and direct sequencing.Results
The allele frequency of rs11646213 was significantly different between the preeclampsia and control groups (P = 0.017, OR = 1.36, 95% CI = 1.06–1.76). Differences were particularly significant in the severe preeclampsia subgroup (P = 0.002, OR = 1.54, 95% CI = 1.17–2.03) and the early-onset preeclampsia subgroup (P = 0.004, OR = 1.57, 95% CI = 1.16–2.13). Genotyping analysis showed that the T allele of rs11646213 could confer a risk for preeclampsia, severe preeclampsia and early-onset preeclampsia.Conclusions
Rs11646213 upstream of the CDH13 gene is associated with preeclampsia in Han Chinese women. 相似文献18.
Sofia I. I. Kring Thomas Werge Claus Holst S?ren Toubro Arne Astrup Torben Hansen Oluf Pedersen Thorkild I. A. S?rensen 《PloS one》2009,4(8)
Background
Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these genes with obesity and metabolic traits.Methodology/Principal Findings
In a population of 166 200 young men examined at the draft boards, obese men (n = 726, BMI≥31.0 kg/m2) and a randomly selected group (n = 831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49). Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat-BMI (OR = 1.08, CI = 1.01–1.16). The SNPs were associated with a number of physiological variables; most importantly 5HT2C rs3813929 T-allele was associated with glucose (OR = 4.56, CI = 1.13–18.4) and acute insulin response (OR = 0.65, CI = 0.44–0.94) in S-49. COMT rs4680 GG-genotype was associated with glucose (OR = 1.04, CI = 1.00–1.09). Except for an association between 5HT2A rs6311 and total-cholesterol at both surveys, significant in S-46 (OR = 2.66, CI = 1.11–6.40), no significant associations were observed for the other phenotypes. Significant associations were obtained when combined genotype of 5HT2C rs3813929 and COMT rs4680 were examined in relation to BMI (OR = 1.12, CI = 1.03–1.21), fat-BMI (OR = 1.22, CI = 1.08–1.38), waist (OR = 1.13, CI = 1.04–1.22), and cholesterol (OR = 5.60, CI = 0.99–31.4). Analyses of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) revealed, a 12.3% increased frequency of 5HT2C rs3813929 T-allele and an 11.6% increased frequency of COMT rs4680 GG-genotype in individuals with IGT or T2D (χ2, p = 0.05 and p = 0.06, respectively). Examination of the combined genotypes of 5HT2C and COMT showed a 34.0% increased frequency of IGT or T2D (χ2, p = 0.01).Conclusions
The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored. 相似文献19.
Anders Borglykke Niels Grarup Thomas Spars? Allan Linneberg Mogens Fenger J?rgen Jeppesen Torben Hansen Oluf Pedersen Torben J?rgensen 《PloS one》2012,7(11)
Aim
To assess the individual and combined effect of 46 type 2 diabetes related risk alleles on incidence of a composite CVD endpoint.Methods
Data from the first Danish MONICA study (N = 3523) and the Inter99 study (N = 6049) was used. Using Cox proportional hazard regression the individual effect of each risk allele on incident CVD was analyzed. Risk was presented as hazard ratios (HR) per risk allele.Results
During 80,859 person years 1441 incident cases of CVD (fatal and non-fatal) occurred in the MONICA study. In Inter99 942 incident cases were observed during 61,239 person years.In the Danish MONICA study four gene variants were significantly associated with incident CVD independently of known diabetes status at baseline; SLC2A2 rs11920090 (HR 1.147, 95% CI 1.027–1.283 , P = 0.0154), C2CD4A rs7172432 (1.112, 1.027–1.205 , P = 0.0089), GCKR rs780094 (1.094, 1.007–1.188 , P = 0.0335) and C2CD4B rs11071657 (1.092, 1.007–1.183 , P = 0.0323). The genetic score was significantly associated with increased risk of CVD (1.025, 1.010–1.041, P = 0.0016). In Inter99 two gene variants were associated with risk of CVD independently of diabetes; SLC2A2 (HR 1.180, 95% CI 1.038–1.341 P = 0.0116) and FTO (0.909, 0.827–0.998, P = 0.0463). Analysing the two populations together we found SLC2A2 rs11920090 (HR 1.164, 95% CI 1.070–1.267, P = 0.0004) meeting the Bonferroni corrected threshold for significance. GCKR rs780094 (1.076, 1.010–1.146, P = 0.0229), C2CD4B rs11071657 (1.067, 1.003–1.135, P = 0.0385) and NOTCH2 rs10923931 (1.104 (1.001 ; 1.217 , P = 0.0481) were found associated with CVD without meeting the corrected threshold. The genetic score was significantly associated with increased risk of CVD (1.018, 1.006–1.031, P = 0.0043).Conclusions
This study showed that out of the 46 genetic variants examined only the minor risk allele of SLC2A2 rs11920090 was significantly (P = 0.0005) associated with a composite endpoint of incident CVD below the threshold for statistical significance corrected for multiple testing. This potential pathway needs further exploration. 相似文献20.
Jing He Yu Xu Li-Xin Qiu Jin Li Xiao-Yan Zhou Meng-Hong Sun Jiu-Cun Wang Ya-Jun Yang Li Jin Qing-Yi Wei Yanong Wang 《PloS one》2012,7(11)