Association of genetic variations in the Wnt signaling pathway genes with myocardial infarction susceptibility in Chinese Han population.
ABSTRACT: Numerous studies have implicated the Wnt pathway in the development and progression of myocardial infarction (MI); however, there are very few investigations addressing the effects of polymorphisms in the Wnt pathway genes on MI susceptibility. We investigated the possible correlation between genetic variations in Wnt pathway genes and MI risk. Three polymorphisms (rs7832767 C > T in SFRP1 gene, rs2293303 C > T in CTNNB1 gene, rs16893344 C > T in WISP1 gene) were finally selected and genotyped in 465 MI patients and 485 healthy controls, using the PCR-RFLP method. We found that the SFRP1 rs7832767 variant allele (T) was associated with a significantly increased risk of MI [TT vs. CC: adjusted odds ratio (AOR) = 3.13, 95% CI = 1.78-5.51; CT/TT vs. CC: AOR = 1.53, 95% CI = 1.12-2.08; TT vs. CC/CT:AOR = 2.87, 95% CI = 1.66-4.97)]. The significant association with MI risk was also found for the CTNNB1 rs2293303 (CT vs. CC: AOR = 3.48, 95% CI = 2.28-5.33; TT vs. CC: AOR = 7.37, 95% CI = 2.08-26.16; CT/TT vs. CC: AOR = 3.72, 95% CI = 2.46-5.62; TT vs. CC/CT:AOR = 5.52, 95% CI = 1.58-19.28), and WISP1 rs16893344 polymorphisms (CT vs. CC: AOR = 2.43, 95% CI = 1.70-3.47; TT vs. CC: AOR = 5.17, 95% CI = 1.85-14.41; CT/TT vs. CC: AOR = 2.58, 95% CI = 1.83-3.66; TT vs. CC/CT:AOR = 3.88, 95% CI = 1.41-10.64). The associations remain significant in stratified analysis by demographic and clinical characteristics of participants, with few exceptions. Our study provided the first evidence of the association between polymorphisms in the Wnt pathway genes and MI susceptibility in Chinese Han population. Epidemiological studies with larger samples and functional analyses are warranted to further verify our results.
Project description:<h4>Background</h4>WNT1-inducible signaling pathway protein 1 (WISP1) is a member of the CCN protein family and a downstream target of β-catenin. Aberrant WISP1 expression may be involved in carcinogenesis. To date, no studies have investigated the association between single-nucleotide polymorphisms (SNPs) of WISP1 and gastric cancer. Therefore, we conducted this study to explore their relationship.<h4>Methods</h4>Polymerase chain reaction-restriction fragment length polymorphism assay was used to analyze three SNPs of WISP1 in 204 gastric cancer patients and 227 controls.<h4>Results</h4>Overall, we could not identify a significant association between WISP1 SNPs and gastric cancer risk. However, the subgroup analysis demonstrated that the presence of the rs7843546 T allele was associated with a significantly decreased risk of gastric cancer in those of Han Chinese ethnicity (CT vs. CC: OR = 0.33, 95%CI 0.14-0.78; TT vs. CC: OR = 0.29, 95%CI 0.11-0.76; CT + TT vs. CC: OR = 0.32, 95%CI 0.14-0.74). In addition, patients with the rs7843546 TT genotype display a 0.34-fold lower risk of developing stage I/II gastric cancer than those with the CC genotype Furthermore, individuals ≥ 50 years old who carried the rs10956697 AC genotype had a significantly decreased risk of gastric cancer (OR = 0.58, 95%CI 0.35-0.98). Smokers with the rs10956697 AC and AC + AA genotypes exhibited a 0.28-fold lower and 0.32-fold lower risk of gastric cancer, respectively.<h4>Conclusions</h4>The WISP1 SNPs rs7843546 and rs10956697 were, for the first time, found to reduce susceptibility to gastric cancer in various subgroups of Guangxi Chinese.
Project description:Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50-0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3-5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41-0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking-related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17-0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking-related cancers among never smokers.
Project description:Oxidative stress is significant in numerous types of cancer. Tobacco smoke, an important risk factor for oral squamous cell carcinoma (OSCC), is able to generate reactive oxygen species (ROS) and cause oxidative DNA damage. Superoxide dismutase (SOD) is an endogenous antioxidant enzyme that is critical in limiting the oxidative burden effectively. The purpose of this study was to investigate the effects of the mitochondrial SOD2 and Cu/Zn enzyme SOD1 gene polymorphisms on the susceptibility to and clinicopathological characteristics of OSCC, as well as the synergistic effect between these gene polymorphisms and the well-known risk factor of tobacco consumption. Patients with clinically diagnosed OSCC (n=362) and healthy normal individuals (n=358) were investigated for four single nucleotide polymorphisms (SNPs; rs4880, rs5746136, rs1804450 and rs11556620) by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. Following adjustment for other confounders, no significant difference was observed in the rs5746136 SOD2 SNPs between the patients and controls. However, the incidence of the CT genotype of SOD2 SNP rs4880 was higher in the patients than in normal subjects in the additive model [CT vs. TT; P=0.045; adjusted odds ratio (AOR)=1.484; 95% confidence interval (CI), 1.009-2.182] and in the dominant model (CT/CC vs. TT; P=0.022; AOR=1.559; 95% CI, 1.067-2.278). For those who smoked, the incidence of the CT genotype of rs4880 increased markedly in the patients compared with the controls in the additive model (CT vs. TT; P=0.003; AOR=2.325; 95% CI, 1.330-4.064) and in the dominant model (CT/CC vs. TT; P=0.001; AOR=2.448; 95% CI, 1.417-4.230). For SOD1, polymorphisms at rs1804450 and rs11556620 were not present in any of the OSCC or control subjects. The results suggest that SOD2 rs4880 may be involved in the tumorigenesis of OSCC and may be useful as a genetic susceptibility marker for OSCC.
Project description:Despite the association between cognitive impairment and delirium, little is known about whether genetic differences that confer cognitive resilience also confer resistance to delirium. To investigate whether older adults without postoperative delirium, compared with those with postoperative delirium, are more likely to have specific single nucleotide polymorphisms (SNPs) in the FKBP5, KIBRA, KLOTHO, MTNR1B, and SIRT1 genes known to be associated with cognition or delirium. This prospective nested matched exploratory case-control study included 94 older adults who underwent orthopedic surgery and screened for postoperative delirium. Forty-seven subjects had incident delirium, and 47 age-matched controls were not delirious. The primary study outcome was genotype frequency for the five SNPs. Compared with participants with delirium, those without delirium had higher adjusted odds of KIBRA SNP rs17070145 CT/TT [vs. CC; adjusted odds ratio (aOR) 2.80, 95% confidence interval (CI) 1.03, 7.54; p = 0.04] and MTNR1B SNP rs10830963 CG/GG (vs. CC; aOR 4.14, 95% CI 1.36, 12.59; p = 0.01). FKBP5 SNP rs1360780 CT/TT (vs. CC) demonstrated borderline increased adjusted odds of not developing delirium (aOR 2.51, 95% CI 1.00, 7.34; p = 0.05). Our results highlight the relevance of KIBRA, MTNR1B, and FKBP5 in understanding the complex relationship between delirium, cognition, and sleep, which warrant further study in larger, more diverse populations.
Project description:<h4>Purpose</h4>To investigate the relationships between Wnt1 inducible signaling pathway protein 1 (WISP1) polymorphisms and the prognosis of platinum-based chemotherapy in lung cancer patients.<h4>Patients and methods</h4>A total of 363 lung cancer patients were recruited in this study. All of them received at least two cycles of platinum-based chemotherapy. We used unconditional logistic regression analysis to assess the associations of 39 single nucleotide polymorphisms in WISP1 gene with platinum-based chemotherapy prognosis.<h4>Results</h4>The results indicated that patients carried rs2929973 GT or GG genotypes had increased risk of disease progression (HR = 0.712, 95% CI = 0.553-0.916, <i>P</i> = 0.015). Patients with rs2977551 TT genotype had a significantly decreased risk of progression-free survival than patients carrying CT or CC genotype (HR = 0.723, 95% CI = 0.561-0.932, <i>P</i> = 0.032) and overall survival (HR = 0.725, 95% CI = 0.552-0.913, <i>P</i> = 0.045). For rs2977549, patients carrying TT genotype had a significantly longer progression-free survival than patients with CC or CT genotypes (HR = 0.708, 95% CI = 0.550-0.912, <i>P</i> = 0.017). Among of them, rs16904853, rs10956697, rs2929965, rs2929973, rs7828685, rs2977551 and rs2977549 were related to progression-free survival, and rs10956697 and rs2977551 were related to overall survival in subgroup analyses, respectively.<h4>Conclusion</h4>WISP1 rs2929973, rs2977551 and rs2977549 may be contributed to a potential candidate biomarker for prediction of platinum-based chemotherapy prognosis in lung cancer patients.
Project description:INTRODUCTION AND OBJECTIVE:Many studies have been conducted on the association between the adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) gene C3435T polymorphism and leukemia risk, however, the previously published findings remain controversial. Thus, a meta-analysis was carried out to accurately evaluate the effect of this polymorphism on leukemia susceptibility. METHODS:A computerized literature search was conducted of PubMed, Elsevier database, the China National Knowledge Infrastructure database, and Wanfang Database, to find published case-control studies exploring the relationship between ABCB1 C3435T polymorphism and leukemia risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of association. RESULTS:A total of 17 studies of 2,431 cases and 3,028 controls were included in this meta-analysis. The results of overall comparisons suggest that there is a significant association between ABCB1 C3435T polymorphism and leukemia risk under two genetic models (TT vs CC: OR=1.39, 95% CI=1.04-1.84, P=0.02; CT+TT vs CC: OR=1.20, 95% CI=1.06-1.36, P=0.004). In the subgroup analyses by ethnicity, age, and leukemia subtype, a significant association was found in Caucasian (CT vs CC: OR=1.22, 95% CI=1.03-1.45, P=0.02; TT vs CC: OR=1.34, 95% CI=1.10-1.64, P=0.004; CT+TT vs CC: OR=1.27, 95% CI=1.08-1.49, P=0.004), adult leukemia (CT vs CC: OR=1.46, 95% CI=1.17-1.83, P=0.001; CT+TT vs CC: OR=1.43, 95% CI=1.01-2.03, P=0.04), and lymphocytic leukemia (TT vs CC: OR=1.73, 95% CI=1.19-2.51, P=0.004; TT vs CC+CT: OR=1.62, 95% CI=1.10-2.38, P=0.01; CT+TT vs CC: OR=1.28, 95% CI=1.10-1.48, P=0.001). CONCLUSION:The meta-analysis suggests that ABCB1 C3435T polymorphism is associated with increased risk of leukemia.
Project description:Associations between vascular endothelial growth factor (VEGF) polymorphisms (rs833061, rs1413711, and rs3025039) and risk of age-related macular degeneration (AMD) have been extensively studied, but the currently available results are contentious rather than conclusive. Therefore, we performed the present meta-analysis to further assess the associations. Literature search in PubMed, Embase, and Web of Science databases was conducted until April 2013. The strength of the associations between VEGF polymorphisms and AMD risk was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Both models of fixed effects and random effects were performed to summarize the pooled ORs. All data were analyzed by Stata software 12.0. The meta-analysis results based on nine case-control studies with 2427 cases and 2037 controls showed that rs833061 had protective effects on AMD risk (TT vs. CT+CC: OR=0.58, 95% CI=0.41-0.81), whereas rs1413711 (TT vs. CT+CC: OR=1.46, 95% CI=1.10-1.93) and rs3025039 (TT vs. CC: OR=1.87, 95% CI=1.15-3.02; TT vs. CT+CC: OR=2.09, 95% CI=1.30-3.37) represented as risk factors for AMD. Subgroup analysis by ethnicity suggested significantly reduced risk in Caucasians (TT vs. CT+CC: OR=0.60, 95% CI=0.36-0.99; T vs. C: OR=0.89, 95% CI=0.78-1.00) and Asians (TT+CT vs. CC: OR=0.57, 95% CI=0.34-0.96; TT vs. CT+CC: OR=0.54, 95% CI=0.33-0.90) for rs833061, yet elevated risk in Caucasians (TT vs. CT+CC: OR=2.05, 95% CI=1.24-3.38) for rs1413711 and in Asians (TT vs. CC: OR=2.06, 95% CI=1.24-3.43; TT vs. CC: OR=2.34, 95% CI=1.42-3.89) for rs3025039. In stratified analysis by type of AMD, rs833061 was observed to decrease wet AMD risk, while rs1413711 and rs3025039 were found to increase the risk of wet AMD. Based on the currently available data, this meta-analysis suggests that the VEGF polymorphisms may be associated with risk of AMD, particularly wet AMD.
Project description:Although many epidemiologic studies have investigated the CYP1A1 MspI gene polymorphisms and their associations with esophageal cancer (EC), definite conclusions cannot be drawn. To clarify the effects of CYP1A1 MspI polymorphisms on the risk of EC, a meta-analysis was performed in Chinese population.Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till October 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations.A total of 13 studies including 1,519 EC cases and 1,962 controls were involved in this meta-analysis. Overall, significant association was found between CYP1A1 MspI polymorphism and EC risk when all studies in the Chinese population pooled into this meta-analysis (C vs. T: OR = 1.25, 95% CI = 1.04 to 1.51; CC + CT vs. TT: OR = 1.35, 95% CI = 1.06 to 1.72; CC vs. TT + CT: OR = 1.35, 95% CI = 1.03 to 1.76). When we performed stratified analyses by geographical locations, histopathology type, and source of control, significantly increased risks were found in North China (C vs. T: OR = 1.38, 95% CI = 1.12 to 1.70; CC vs. TT: OR = 1.72, 95% CI = 1.16 to 2.56; CC + CT vs. TT: OR = 1.52, 95% CI = 1.14 to 2.02; CC vs. TT + CT: OR = 1.55, 95% CI = 1.17 to 2.06), in the population-based studies (C vs. T: OR = 1.22, 95% CI = 1.05 to 1.42; CC vs. TT: OR = 1.38, 95% CI = 1.02 to 1.88; CC + CT vs. TT: OR = 1.36, 95% CI = 1.10 to 1.69; CC vs. TT + CT: OR = 1.43, 95% CI = 1.13 to 1.81) and ESCC (C vs. T: OR = 1.17, 95% CI = 1.04 to 1.32; CC + CT vs. TT: OR = 1.28, 95% CI = 1.08 to 1.52).This meta-analysis provides the evidence that CYP1A1 MspI polymorphism may contribute to the EC development in the Chinese population.
Project description:BACKGROUND:Previous genome-wide association studies have identified a link between the rs13041247 single nucleotide polymorphisms (SNPs) in the chromosome 20q12 locus and the development of the congenital malformation known as nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present meta-analysis was therefore designed to formally assess the relationship between rs13041247 and NSCL/P. METHODS:We searched Embase, Web of Science, PubMed, the China National Knowledge Internet (CNKI), and the China Wanfang database in order to identify relevant published through 25 June 2019. This allowed us to identify 13 studies incorporating 4914 patients and 5981 controls for whom rs13041247 genotyping had been conducted, with STATA 12.0 then being used to conduct a meta-analysis of these pooled results. The I2 statistic was used to compare heterogeneity among studies. RESULTS:In total this analysis incorporated 13 case-control studies. No association between the rs13041247 polymorphism and NSCL/P risk was detected in individuals of Asian ethnicity (C vs T: OR?=?0.847, 95% CI?=?0.702-1.021; CC vs TT: OR?=?0.725, 95% CI?=?0.494-1.063; CC vs CT: OR?=?0.837, 95% CI?=?0.657-1.067; CT?+?TT vs CC: OR?=?1.265, 95% CI?=?0.951-1.684; CC?+?CT vs TT: OR?=?0.805, 95% CI?=?0.630-1.029) or Caucasian ethnicity (C vs T: OR?=?0.936, 95% CI?=?0.786-1.114; CC vs TT: OR?=?0.988, 95% CI?=?0.674-1.446; CC vs CT: OR?=?1.197, 95% CI?=?0.816-1.757; CT?+?TT vs CC: OR?=?0.918, 95% CI?=?0.639-1.318; CC?+?CT vs TT: OR?=?0.855, 95% CI?=?0.677-1.081). However, an overall analysis of all participants in these studies revealed the rs13041247 C allele, the CT genotype, and the CC?+?CT model to be linked to a reduced NSCL/P risk (C vs T: OR?=?0.897, 95% CI: 0.723-1.114, P?=?0.048; CT vs TT: OR?=?0.839, 95% CI: 0.734-0.959, P?=?0.01; CC?+?CT vs TT: OR?=?0.824, 95% CI: 0.701-0.968, P?=?0.019). CONCLUSION:These results suggest that the rs13041247 SNP located at the 20q12 chromosomal locus is associated with NSCL/P risk in an overall pooled study population, although this association was not significant in East Asian or Caucasian populations.
Project description:To investigate the association of programmed death-1 gene polymorphism rs2227981 with tumor risk. The PubMed, Medline, Ovid Medline, EMBASE, Web of Knowledge were searched. Meta-analyses were conducted using RevMan 5.2.2 software. Total six researches involving in a total of 1427 tumor patients and 1811 healthy control people were included into this meta analysis. There was no association of PD-1 gene polymorphism with total tumor risk under four genetic models. (CT+TT vs CC, OR=1.09, 95% CI=0.80-1.49, P=0.59; CT+CC vs TT, OR=0.93, 95% CI=0.52-1.66, P=0.61; TT vs CC, OR=0.99, 95% CI=0.57-1.72, P=0.97; CT vs CC, OR=1.16, 95% CI=0.80-1.70, P=0.43). The sub-group analysis shown there were a significantly difference on association of PD-1 gene polymorphism with digestive system tumor risk between tumor patients and healthy control people, except recessive model. (CT+TT vs CC, OR=1.57, 95% CI=1.20-2.07, P=0.001; TT vs CC, OR=1.67, 95% CI=1.12-2.49, P=0.01; CT vs CC, OR=1.51, 95% CI=1.13-2.01, P=0.005). Moreover, the meta analysis results shown that there were association of PD-1 gene polymorphism with tumor risk under two models for the tumor specific occurring only in women. (CT+TT vs CC, OR=0.80, 95% CI=0.67-0.95, P=0.01; TT vs CC, OR=0.61, 95% CI=0.44-0.83, P=0.002). This study suggests that PD-1 gene polymorphism rs2227981 is associated with specific tumor types, including digestive system tumor and tumor specific occurring in woman.