Dataset Information

Associations between LMO1 gene polymorphisms and central nervous system tumor susceptibility.

ABSTRACT:

Importance

LIM domain only 1 (LMO1) gene polymorphisms were previously found to be implicated in the risk of several cancers. No available studies were performed regarding the predisposing effect of LMO1 gene single nucleotide polymorphisms (SNPs) on central nervous system (CNS) tumor risk.

Objective

We aimed to determine whether the LMO1 gene SNPs were associated with the risk of CNS tumor by applying a case-control study with 191 cases and 248 controls in China.

Methods

The contributions of LMO1 gene SNPs to the risk of CNS tumor was evaluated by multinomial logistic regression.

Results

Based on the calculations of odds ratio (OR) and 95% confidence interval (CI), we failed to detect a significant relationship between each LMO1 gene SNP (rs110419 A>G, rs4758051 G>A, rs10840002 A>G, rs204938 A>G, and rs2168101 G>T) and CNS tumor risk, respectively. A negative association was also found in the combined effects on these five SNPs and CNS tumor risk. The stratification analysis further demonstrated the individuals with rs204938 AG/GG genotype confer to increased risk of CNS tumor compared with those with an AA genotype in males (OR: 1.74, 95% CI: 1.01-2.98, P = 0.046).

Interpretation

We concluded that LMO1 gene SNPs may not strong enough to influence the risk of CNS tumor in Chinese children. More studies are required to verify this association.

SUBMITTER: Lin H

PROVIDER: S-EPMC8666933 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Associations between <i>LMO1</i> gene polymorphisms and central nervous system tumor susceptibility.

Lin Huiran H Chen Huitong H Lin Ao A Liu Xiaoping X Huang Xiaokai X Zhou Jingying J Yuan Li L Zhuo Zhenjian Z

Pediatric investigation 20210821 4

<h4>Importance</h4>LIM domain only 1 (<i>LMO1</i>) gene polymorphisms were previously found to be implicated in the risk of several cancers. No available studies were performed regarding the predisposing effect of <i>LMO1</i> gene single nucleotide polymorphisms (SNPs) on central nervous system (CNS) tumor risk.<h4>Objective</h4>We aimed to determine whether the <i>LMO1</i> gene SNPs were associated with the risk of CNS tumor by applying a case-control study with 191 cases and 248 controls in Ch ...[more]

PMID: 34938970

Similar Datasets

Project description:Importance:Recent studies found that the concentration of amyloid-? (A?) fluctuates with the sleep-wake cycle. Although the amplitude of this day/night pattern attenuates with age and amyloid deposition, to our knowledge, the association of A? kinetics (ie, production, turnover, and clearance) with this oscillation has not been studied. Objective:To determine the association between A? kinetics, age, amyloid levels, and the A? day/night pattern in humans. Design, Setting, and Participants:We measured A? concentrations and kinetics in 77 adults aged 60 to 87 years with and without amyloid deposition by a novel precise mass spectrometry method at the Washington University School of Medicine in St Louis, Missouri. We compared findings of 2 orthogonal methods, enzyme-linked immunosorbent assay and mass spectrometry, to validate the day/night patterns and determine more precise estimates of the cosinor parameters. In vivo labeling of central nervous system proteins with stable isotopically labeled leucine was performed, and kinetics of A?40 and A?42 were measured. Interventions:Serial cerebrospinal fluid collection via indwelling lumbar catheter over 36 to 48 hours before, during, and after in vivo labeling, with a 9-hour primed constant infusion of 13C6-leucine. Main Outcomes and Measures:The amplitude, linear increase, and other cosinor measures of each participant's serial cerebrospinal fluid A? concentrations and A? turnover rates. Results:Of the 77 participants studied, 46 (59.7%) were men, and the mean (range) age was 72.6 (60.4-87.7) years. Day/night patterns in A? concentrations were more sharply defined by the precise mass spectrometry method than by enzyme-linked immunosorbent assay (mean difference of SD of residuals: A?40, -7.42 pM; P?<?.001; A?42, -3.72 pM; P?<?.001). Amyloid deposition diminished day/night amplitude and linear increase of A?42 but not of A?40. Increased age diminished day/night amplitude of both A?40 and A?42. After controlling for amyloid deposition, amplitude of A?40 was positively associated with production rates (r?=?0.42; P?<?.001), while the linear rise was associated with turnover rates (r?=?0.28; P?<?.05). The amplitude and linear rise of A?42 were both associated with turnover (r?=?-0.38; P?<?.001) and production (r?=?0.238; P?<?.05) rates. Conclusions and Relevance:Amyloid deposition is associated with premature loss of normal A?42 day/night patterns in older adults, suggesting the previously reported effects of age and amyloid on A?42 amplitude at least partially affect each other. Production and turnover rates suggest that day/night A? patterns are modulated by both production and clearance mechanisms active in sleep-wake cycles and that amyloid deposition may impair normal circadian patterns. These findings may be important for the designs of future secondary prevention trials for Alzheimer disease.

Project description:Vitamin D3 (VitD) insufficiency is postulated to represent a major modifiable risk factor for multiple sclerosis (MS). While low VitD levels strongly correlate with higher MS risk in white populations, this is not the case for other ethnic groups, suggesting the existence of a genetic component. Moreover, VitD supplementation studies in MS so far have not shown a consistent benefit. We sought to determine whether direct manipulation of VitD levels modulates central nervous system autoimmune disease in a sex-by-genotype-dependent manner. To this end, we used a dietary model of VitD modulation, together with the autoimmune animal model of MS, experimental autoimmune encephalomyelitis (EAE). To assess the impact of genotype-by-VitD interactions on EAE susceptibility, we utilized a chromosome substitution (consomic) mouse model that incorporates the genetic diversity of wild-derived PWD/PhJ mice. High VitD was protective in EAE in female, but not male C57BL/6J (B6) mice, and had no effect in EAE-resistant PWD/PhJ (PWD) mice. EAE protection was accompanied by sex- and genotype-specific suppression of proinflammatory transcriptional programs in CD4 T effector cells, but not CD4 regulatory T cells. Decreased expression of proinflammatory genes was observed with high VitD in female CD4 T effector cells, specifically implicating a key role of MHC class II genes, interferon gamma, and Th1 cell-mediated neuroinflammation. In consomic strains, effects of VitD on EAE were also sex- and genotype dependent, whereby high VitD: (1) was protective, (2) had no effect, and (3) unexpectedly had disease-exacerbating effects. Systemic levels of 25(OH)D differed across consomic strains, with higher levels associated with EAE protection only in females. Analysis of expression of key known VitD metabolism genes between B6 and PWD mice revealed that their expression is genetically determined and sex specific and implicated Cyp27b1 and Vdr as candidate genes responsible for differential EAE responses to VitD modulation. Taken together, our results support the observation that the association between VitD status and MS susceptibility is genotype dependent and suggest that the outcome of VitD status in MS is determined by gene-by-sex interactions.

Project description:ImportanceTumor necrosis factor (TNF) inhibitors are common therapies for certain autoimmune diseases, such as rheumatoid arthritis. An association between TNF inhibitor exposure and inflammatory central nervous system (CNS) events has been postulated but is poorly understood.ObjectiveTo evaluate whether TNF inhibitor exposure is associated with inflammatory demyelinating and nondemyelinating CNS events in patients with an indication for TNF inhibitor use and to describe the spectrum of those CNS events.Design, setting, and participantsA nested case-control study was conducted using the medical records of patients with autoimmune diseases treated at 3 Mayo Clinic locations (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida) between January 1, 2003, and February 20, 2019. Patients were included if their records reported International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnostic codes for US Food and Drug Administration-approved autoimmune disease indication for TNF inhibitor use (ie, rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, Crohn disease, and ulcerative colitis) and diagnostic codes for inflammatory CNS events of interest. Patients were matched 1:1 with control participants by year of birth, type of autoimmune disease, and sex.ExposuresTNF inhibitor exposure data were derived from the medical records along with type of TNF inhibitor, cumulative duration of exposure, and time of exposure.Main outcomes and measuresThe main outcome was either inflammatory demyelinating (multiple sclerosis and other diseases such as optic neuritis) or nondemyelinating (meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis) CNS event. Association with TNF inhibitor was evaluated with conditional logistic regression and adjusted for disease duration to determine the odds ratios (ORs) and 95% CIs. Secondary analyses included stratification of outcome by inflammatory demyelinating and nondemyelinating CNS events and by autoimmune disease (rheumatoid arthritis and non-rheumatoid arthritis).ResultsA total of 212 individuals were included: 106 patients with inflammatory CNS events and 106 control participants without such events. Of this total, 136 were female (64%); the median (interquartile range) age at disease onset for patients was 52 (43-62) years. Exposure to TNF inhibitors occurred in 64 patients (60%) and 42 control participants (40%) and was associated with an increased risk of any inflammatory CNS event (adjusted OR, 3.01; 95% CI, 1.55-5.82; P = .001). These results were similar when the outcome was stratified by demyelinating and nondemyelinating CNS events. Secondary analyses found the association was predominantly observed in patients with rheumatoid arthritis (adjusted OR, 4.82; 95% CI, 1.62-14.36; P = .005).Conclusions and relevanceThis study found that exposure to TNF inhibitors in patients with autoimmune diseases appeared to be associated with increased risk for inflammatory CNS events. Whether this association represents de novo or exacerbated inflammatory pathways requires further research.