Two-center Case-control Study Research Articles

Retracted: SOCS3 Gene Polymorphism and Hypertension Susceptibility in Chinese Population: A Two-Center Case-Control Study.

[This retracts the article DOI: 10.1155/2021/8445461.].

Increased Risk of Neurological Disease Following Pediatric Rotavirus Infection: A Two-Center Case-Control Study.

Whether pediatric rotavirus infection is associated with extraintestinal complications remains unknown. We conducted a case-control study to investigate the incidences and risks of rotavirus-associated extraintestinal complications in hospitalized newborns, infants, and children younger than 5 years. A total of 1325 young inpatients with rotavirus infection (754 male and 539 newborns) and 1840 controls without rotavirus infection (1035 male and 836 newborns) were included. The incidences of neurological disease were higher among rotavirus individuals compared with controls: newborns, 7.24% (39/539) versus 2.87% (24/836), P < .001; infants and young children, 19.59% (154/786) versus 12.35% (124/1004), P < .001. The associated odd ratios (ORs) for neurological disease frequency following rotavirus infection was 2.64 (95% confidence interval [CI], 1.57-4.44) for newborns and 1.73 (95% CI, 1.34-2.24) for infants and young children, which increased to 2.56 (95% CI, 1.57-4.18) in case-control (1:1) matching analysis and 1.85 (95% CI, 1.41-2.42) in confounder adjustment. Rotavirus infection was associated with other extraintestinal complications, depending on study population and disease severity. Outcome analysis revealed rotavirus infection and its consequences had a significant impact on hospitalization and discharge. Rotavirus exposure was associated with a spectrum of extraintestinal complications, particularly neurological disease. Rotavirus infection and subsequent consequences resulted in poor clinical outcomes.

Plasma acylcarnitine and diabetic retinopathy: A study from Eastern China.

Acylcarnitines (ACars) are important for insulin resistance and type 2 diabetes (T2D). However, their roles in diabetic retinopathy (DR) remain controversial. In this study, we aimed to investigate the association of ACars with DR and their values in DR detection. This was a two-center case-control study based on the propensity score matching approach between August 2017 to June 2018 in Eastern China. Multivariable logistic regression models were applied to estimate the association of plasma ACars with DR. Differential ACars were screened by models of least absolute shrinkage and selection operator, elastic net, and weighted quantile sum regression, and their roles in DR identification were further evaluated by the area under the receiver operating curve (AUC). Eight of twenty plasma ACars (8:0, 12:0, 12:1, 14:1, 16:2, 18:0, 18:2 and 18:3) were associated with DR, while only ACar 8:0 was selected by three variable selection methods. As compared to those with the 1st tertile of ACar 8:0, the adjusted odds ratio (OR) and 95% confidence interval (CI) of DR were 0.22 (0.08, 0.59) and 0.12 (0.04, 0.36) for subjects in the 2nd and 3rd tertiles, respectively (P for trend < 0.001). Consistent associations were also observed in both restricted cubic spline regression models and subgroup analyses. AUC (95% CI) were 0.74 (0.66, 0.82) for ACar 8:0 alone and 0.77 (0.70, 0.85) for ACar 8:0 combined with covariates. Our findings suggest higher ACar 8:0 is significantly associated with a decreased risk of DR, which provides a unique window for early identification of DR.

Enhanced Recovery after Surgery (ERAS) in DIEP-Flap Breast Reconstructions-A Comparison of Two Reconstructive Centers with and without ERAS-Protocol.

Enhanced recovery after surgery (ERAS) is established for autologous breast reconstruction. ERAS leads to a shortened hospital stay and improved outcome after elective surgery. In this retrospective, two-center case–control study, we compared two different treatment regimens for patients undergoing a DIEP-flap breast reconstruction from two centers, one with an established ERAS protocol and one without. All patients with DIEP breast reconstructions over the period of 12 months were included. The primary outcome measure was the length of hospital stay (LOS) in days. A total of 79 patients with 95 DIEP-flaps were analyzed. In group A (ERAS) 42 patients were operated with DIEP flaps, in group B (non-ERAS) 37 patients. LOS was significantly reduced in the ERAS group (4.51 days) compared to the non-ERAS group (6.32; p < 0.001). Multivariate analysis showed that, in group A, LOS is significantly affected by surgery duration. BMI in the ERAS group had no effect on LOS. In group B a higher BMI resulted in a significantly higher LOS. In multivariate analysis, neither age nor type for surgery (primary/secondary/after neoadjuvant therapy, etc.) affected LOS. In both groups, no systemic or flap-related complications were observed. Comparing two reconstructive centers with and without implemented ERAS, ERAS led to a significantly decreased LOS for all patients. ERAS implementation does not result in an increased complication rate or flap loss. Postoperative pain can be well managed with basic analgesia using NSAID when intraoperative blocks are applied. The reduced use of opioids was well tolerated. With implementation of ERAS the recovery experience can be enhanced making autologous breast reconstructions more available and attractive for various patients.

Plasma Lipocalin 2 in Alzheimer\u2019s disease: potential utility in the differential diagnosis and relationship with other biomarkers

BackgroundLipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer’s disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer’s disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer’s disease, differential diagnoses, other biomarkers, and clinical data.MethodsFor this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer’s disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer’s disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28).ResultsPlasma Lipocalin-2 was significantly lower in Alzheimer’s disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer’s pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer’s disease and healthy controls were 0.783 (95%CI: 0.712–0.855) in the study cohort and 0.766 (95%CI: 0.627–0.905) in the validation cohort. The area under the curve for Alzheimer’s disease versus vascular dementia was 0.778 (95%CI: 0.667–0.890) in the study cohort. In Alzheimer’s disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with non-rapidly progressive Alzheimer’s disease (p = 0.013).ConclusionsPlasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer’s disease and seems to be independent from currently employed biomarkers.

SOCS3 Gene Polymorphism and Hypertension Susceptibility in Chinese Population: A Two-Center Case-Control Study.

Endothelial inflammation and vascular damage are essential risk factors contributing to hypertension. Suppressor of cytokine signaling 3 (SOCS3) is involved in the regulation of multiple inflammatory pathways. A large number of studies have shown that the anti-inflammatory effect of SOCS3 in hypertension, obesity, and allergic reactions has brought more insights into the inhibition of inflammation. Therefore, we selected a tagSNP of SOCS3 (rs8064821) to investigate whether they are contributing to the risk of hypertension in the Chinese population. In total, 532 patients with hypertension and 569 healthy controls were enrolled for two central of China. SOCS3 rs8064821 C>A polymorphism was genotyped using TaqMan assay. SOCS3 rs8064821 CA genotype was associated with an increased risk of hypertension (OR = 1.821, 95%CI = 1.276-2.600, P = 0.001). Rs8064821 A allele was associated with higher SOCS3 mRNA level in PBMCs from healthy donors. SOCS3 rs8064821 C>A polymorphism may contribute to the risk of hypertension in the Chinese population by regulating the expression of SOCS3.

Serum ceramide concentrations are associated with depression in patients after ischemic stroke-A two-center case-controlled study

Background and aimsThe present study aims to correlate the severity of post-stroke depression (PSD) and serum ceramide concentration. Materials and methodsIn this two-center case-control study, we prospectively collected clinical and demographical information from age and gender-matched 51 PSD patients, 56 non-post-stroke depression (Non-PSD) patients, and 39 patients with major depression (MD) to perform the suitable biochemical analysis to bring a correlation in causing depression in patients soon after the stroke. The ROC curve method was used to evaluate ceramide’s diagnostic efficacy in all three groups of patients. A follow-up analysis was also conducted based on PSD severity to associate serum ceramide levels and neuropsychiatric symptoms. The severity of the patient's depressive symptoms was assessed by using the self-rating depression scale (SDS). ResultsIn comparison between PSD and MD patients, three serum ceramide species were found to be significantly different. Compared with Non-PSD patients, PSD patients had significantly higher levels of all the four serum ceramides, and increasing levels ofC16:0, C18:0(VS MD) and C16: 0(VS Non-PSD) serve as a diagnostic tool and an independent risk factor in all three categories of patients. Moreover, the follow-up analysis results showed that, as the treatment progressed, the differences in the 3 serum ceramide species were statistically significant. ConclusionThere was a stage-specific association between serum ceramides and PSD, and the potential pathophysiological mechanism has to be investigated in future research.

KRAS gene polymorphisms are associated with the risk of glioma: a two-center case-control study.

BackgroundGlioma, also known as neuroglioma, is the most common primary tumors of the central nervous system. Many previous studies have reported associations between RAS gene polymorphisms and multiple tumors. However, the role of RAS gene polymorphisms on glioma risk has not been investigated.MethodsWe conducted a two-center case-control study to investigate whether the RAS gene polymorphisms predispose individuals to gliomas in 248 healthy controls and 191 glioma patients. RAS gene polymorphisms (rs12587 G>T, rs7973450 A>G, rs7312175 G>A in KRAS, rs2273267 A>T in NRAS) were genotyped by the TaqMan assay. The relationship between RAS gene functional single nucleotide polymorphisms (SNPs) and the risk of glioma was evaluated based on odds ratios (ORs) and 95% confidence intervals (CIs).ResultsIndividuals with KRAS rs7312175 GA genotype were more likely to develop glioma than those with GG genotype (adjusted OR =1.66, 95% CI: 1.05–2.64, P=0.030). However, the other three SNPs could not affect glioma risk. In stratified analysis of age, gender, subtypes, and clinical stages, rs7312175 GA carriers were more likely to develop glioma in the following subgroups: children less than 60 months, tumor derived from the astrocytic tumors, and clinical stages I.ConclusionsThe study showed that polymorphism rs7312175 GA in the KRAS gene was associated with increased glioma susceptibility. Further investigation is warranted to confirm these findings and to better elucidate the involved biological pathways.

The Association of Polymorphisms in Base Excision Repair Genes with Ovarian Cancer Susceptibility in Chinese Women: A Two-Center Case-Control Study.

Base excision repair (BER) acts upon the most important mechanism of the DNA repair system, protecting DNA stability and integrity from the mutagenic and cytotoxic effects. Multiple researches have indicated that single-nucleotide polymorphisms (SNPs) in the BER-related gene may be associated with the susceptibility of ovarian cancer. However, the results are controversial. In this two-center case-control study, 19 potentially functional SNPs in six BER-related genes (hOGG1, APE1, PARP1, FEN1, LIG3 and XRCC1) was genotyped in 196 ovarian cancer cases and 272 cancer-free controls. And, their associations with ovarian cancer risk were assessed by unconditional logistic regression analyses. We found that PARP1 rs8679 and hOGG1 rs293795 polymorphisms were associated with a decreased risk of ovarian cancer under dominant model (adjusted OR=0.39, 95% CI=0.17-0.90, P=0.026; and adjusted OR=0.36, 95% CI=0.13-0.99, P=0.049, respectively). Stratification analysis demonstrated that this association was more pronounced in the subgroups of lower BMI and patients with early menarche and serous carcinoma. Moreover, LIG3 rs4796030 AA/AC variant genotypes performed an increased risk of ovarian cancer under recessive model (adjusted OR=1.54, 95% CI=1.01-2.35, P=0.046), especially in the subgroups of higher BMI, early clinic stage and the carcinoma at the left. These results suggested that PARP1, hOGG1 and LIG3 polymorphisms might impact on the risk of ovarian cancer. However, more researches with larger and different ethnic populations are warranted to support our findings.

Serum Ω-6/Ω-3 Polyunsaturated Fatty Acids Ratio and Identification of Diabetic Retinopathy: A Propensity Score Matching Based Case-Control Study in China

Background: Optimal ω-6/ω-3 polyunsaturated fatty acids ratio (PUFAR) is reported to exert protective effects against chronic diseases. However, data on PUFAR and diabetic retinopathy (DR) are scarce. We aimed to thoroughly quantify how PUFAR was associated with DR as well as its role in DR detection. Methods: This is a two-center case-control study, patients were matched using a propensity score algorithm. Multivariable logistic regression models and restricted cubic spline analyses were used to examine the association of PUFAR with DR after adjusting for confounders, which were screened by directed acyclic graph. Performance of the predictive ability to identify DR with PUFAR was assessed by receiver operating characteristic (ROC) analysis and Hosmer-Lemeshow test. Findings: An apparent negative relationship between PUFAR and DR was observed. Adjusted likelihood of DR decreased by 79% (OR:0.21, 95% CI:0.10-0.40) with per interquartile range of PUFAR elevation. Similar results were also obtained in tertile analysis. As compared to those in the 1st tertile of PUFAR, the adjusted odds of DR decreased by 76% (OR:0.24, 95% CI:0.08-0.66) and 93% (OR:0.07, 95% CI:0.03-0.22) for subjects in the 2nd and 3rd tertiles, respectively. Good calibration and discrimination of the predictive model were detected and consistent in both training and testing sets, and PUFAR=35 would be an ideal cut-off value for DR identification. Interpretation: Our present study shows that serum PUAFR was inversely associated with DR and could serve as an ideal biomarker in distinguishing DR from type 2 diabetes. Funding: This study was funded by Natural Science Foundation of Zhejiang Province, Zhejiang Basic Public Welfare Research Project, the Major Project of the Eye Hospital of Wenzhou Medical University and the academician’s science, and technology innovation program in Zhejiang province. Part of this work was also funded by the National Nature Science Foundation of China and Science and Research Funding Project for College Students in Wenzhou Medical University. Declaration of Interest: We declare no conflicts of interests. Ethical Approval: The protocol had been carefully reviewed and approved by the Ethic committee of the Eye hospital of Wenzhou medical university before the study (Number: KYK [2017] 46).

Two variants of Interleukin-1B gene are associated with the decreased risk, clinical features, and better overall survival of colorectal cancer: a two-center case-control study.

Interleukin (IL)-1B reportedly promotes the stemness and invasiveness of colon cancer cells. Several studies have investigated the association between IL-1B gene polymorphisms and colorectal cancer (CRC) risk, but report conflicting findings. Here, this association was explored in a hospital-based case-control study involving 527 CRC cases and 639 controls from two Chinese Han populations. Genotyping was done by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The IL-1B expression in CRC patients and controls were obtained from the GEPIA database and the mRNA expressions of different genotypes were downloaded from the GTEx portal database. The relationship of two IL-1B gene loci with clinical parameters and overall survival were analyzed using the Chi-square test and Kaplan-Meier analysis with the log-rank test respectively. It was found that the IL-1B mRNA levels in CRC patients were significantly higher than in controls. Bioinformatic analysis suggested that rs1143634 and rs1143623 polymorphisms decreased the IL-1B mRNA expression. The two polymorphisms were associated with decreased risk for CRC. Stratified analyses revealed the IL-1B gene rs1143623 and rs1143634 polymorphisms decreased the risk of CRC among females, smokers and drinkers. Moreover, the CC and/or GC genotype of rs1143623 polymorphism were correlated with decreased risk among CRC patients with tumor size ≥5cm, TNM stage III+IV, and rectal cancer. For rs1143634 polymorphism, the CT genotype reduced the risk of colorectal adenocarcinoma. The CRC patients carrying CC genotype of rs1143623 polymorphism were associated with better overall survival. In conclusion, IL-1B gene rs1143623 and rs1143634 polymorphisms are associated with decreased risk for CRC patients and thereby play important roles in the etiology of CRC.

Lack of associations between AURKA gene polymorphisms and neuroblastoma susceptibility in Chinese children.

Previous studies have demonstrated that polymorphisms in the AURKA gene are associated with various types of cancer. In neuroblastoma, AURKA protein product regulates N-myc protein levels and plays a critical role in tumorigenesis. To investigate the association between three AURKA polymorphisms (rs1047972 C>T, rs2273535 T>A, and rs8173 G>C) and neuroblastoma susceptibility in Chinese populations, we performed this two-center case–control study including 393 neuroblastoma cases and 812 controls. Two study populations were recruited from two different regions in China. No significant associations were identified amongst any of the three AURKA polymorphisms and the risk of neuroblastoma. Similar observations were found in the stratified analysis. In conclusion, our results indicate that none of the AURKA polymorphisms are associated with neuroblastoma susceptibility in two distinct Chinese populations. Further studies with larger sample sizes and different ethnicities are warranted to validate our results.

Association of Common Genetic Variants in Pre-microRNAs and Neuroblastoma Susceptibility: A Two-Center Study in Chinese Children

Neuroblastoma is a commonly occurring extracranial pediatric solid tumor without defined etiology. Polymorphisms in pre-miRNAs have been demonstrated to associate with the risk of several cancers. So far, no such polymorphism has been investigated in neuroblastoma. With this in mind, we performed a two-center case-control study to assess the association of genetic variants in pre-miRNAs and neuroblastoma susceptibility in Chinese children, including 393 cases and 812 controls. We found that miR-34b/c rs4938723 T > C polymorphism was significantly associated with decreased neuroblastoma risk (TC versus TT: adjusted odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.39–0.67; TC/CC versus TT: adjusted OR = 0.62, 95% CI = 0.48–0.79). We also observed the significant association between the miR-218 rs11134527 A > G polymorphism and decreased neuroblastoma risk (AG versus AA: adjusted OR = 0.73, 95% CI = 0.56–0.96). Stratified analysis further demonstrated that the protective effect of the rs4938723 T > C polymorphism remained prominent in the subgroups, regardless of age, gender, and clinical stages. In term of sites of origin, this polymorphism significantly reduced the risk of tumors originating from the adrenal gland. We further validated the significant results using false-positive report probability analyses. Overall, the miR-34b/c rs4938723 T > C and miR-218 rs11134527 A > G polymorphisms displayed a protective role from neuroblastoma. These findings need further validation.

XPA gene polymorphisms and risk of neuroblastoma in Chinese children: a two-center case-control study.

Neuroblastoma is a malignant tumor arising from the developing sympathetic nervous system, which mainly affects children. Variations in XPA gene have been shown to confer cancer susceptibility. However, no investigation has been reported regarding the association between XPA polymorphisms and neuroblastoma risk. This study was conducted to measure the association of XPA polymorphisms with neuroblastoma susceptibility in Chinese children. In this hospital-based case-control study with 393 cases and 812 controls, we genotyped two polymorphisms (rs1800975 T>C, and rs3176752 G>T) in XPA gene to access their contributions to neuroblastoma risk by TaqMan methods. The strength of the association with neuroblastoma risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs). No single polymorphism was found to predispose to neuroblastoma susceptibility. When risk genotypes were combined, we found that carriers of 1-2 risk genotypes had significantly increased neuroblastoma risk (adjusted OR=1.28; 95% CI=1.001-1.64, P=0.049), when compared to non-carriers. Stratification analysis by age, gender, sites of origin and clinical stages failed to show any significant association. Our study provides cues that XPA gene polymorphisms may exert a weak effect in neuroblastoma risk. This finding needs further validations by larger sample size studies.

Association between NEFL Gene Polymorphisms and Neuroblastoma Risk in Chinese Children: A Two-Center Case-Control Study.

Neuroblastoma is a lethal tumor that mainly occurs in children. To date, the genetic etiology of sporadic neuroblastoma remains obscure. A previous study identified three neuroblastoma susceptibility loci (rs11994014 G>A, rs2979704 T>C, rs1059111 A>T) in neurofilament light (NEFL) gene. Here, we attempted to evaluate the contributions of these three single nucleotide polymorphisms to neuroblastoma susceptibility in Chinese children. We genotyped these three polymorphisms using subjects from Guangdong province (256 cases and 531 controls) and Henan province (118 cases and 281 controls). Logistic regression models were performed to generate odds ratios and 95% confidence intervals to access the association of these three polymorphisms with neuroblastoma risk. Overall, we failed to provide any evidence supporting the association between these three polymorphisms and neuroblastoma susceptibility, either in single center population or in the combined population. Moreover, such null association was also observed when the samples were stratified by age, gender, tumor sites, and clinical stages. In the future, larger samples from different ethnicities are needed to clarify the role of NEFL gene polymorphisms in neuroblastoma risk.

LMO1 polymorphisms reduce neuroblastoma risk in Chinese children: a two-center case-control study.

Previous genome-wide association and validation studies suggest that LIM domain only 1 (LMO1) gene polymorphisms affect neuroblastoma susceptibility. In this work, we used Taqman methodology to genotype four LMO1 polymorphisms (rs110419 A > G, rs4758051 G > A, rs10840002 A > G and rs204938 A > G) in 118 neuroblastoma cases and 281 controls from Northern China. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association. We found that rs4758051 G > A was associated with a decreased neuroblastoma risk (AA vs. GG: adjusted OR = 0.28, 95% CI = 0.13–0.62; AG/AA vs. GG: adjusted OR = 0.62, 95% CI = 0.40–0.97; AA vs. GG/AG: adjusted OR = 0.33, 95% CI = 0.15–0.69). Likewise, carrying the rs10840002 G allele was also associated with a decreased neuroblastoma risk in this Northern Chinese population. In a combination analysis using Southern and Northern Chinese populations, we found that those carrying the rs110419 G, rs4758051 A or rs10840002 G allele were at decreased neuroblastoma risk, and this finding was supported by a false-positive report probability analysis. These results further verify that LMO1 polymorphisms are protective against neuroblastoma. Case-control studies with larger samples and using other ethnicities are still needed to confirm our conclusion.

The role of WWOX polymorphisms on COPD susceptibility and pulmonary function traits in Chinese: a case-control study and family-based analysis.

Single nucleotide polymorphisms (SNPs) in the WW domain containing oxidoreductase (WWOX) gene were recently identified to be quantitative trait loci for lung function and thus likely to be susceptible biomarkers for COPD. However, the associations between WWOX SNPs and COPD risk are still unclear. Here, by conducting a two-center case-control study including 1511 COPD cases and 1677 controls and a family-based analysis comprising 95 nuclear pedigrees, we tested the associations between five SNPs that are rs10220974C >T, rs3764340C >G, rs12918952G >A, rs383362G >T, rs12828G >A of WWOX and COPD risk as well as the hereditary inclination of these loci among COPD families. We found that the SNP rs383362G >T was significantly associated with an increased risk of COPD in a T allele-number dependent-manner (OR = 1.30, 95%CI = 1.11 - 1.52). The T allele was more prone to over transmit to sick children and sibs than the G allele (Z = 2.900, P = 0.004). Moreover, the forced expiratory volume in one second/forced vital capacity (FEV1/FVC), FEV1/predicted-FEV1 and annual FEV1 also significantly decreased in the rs383362T carriers compared to the rs383362GG carriers. For other SNPs, no significant association was observed for COPD and pulmonary function. Taken together, our data demonstrated that the SNP rs383362G >T of WWOX plays a role in COPD inheritance.