A longitudinal study of gene expression in healthy individuals

Karlovich, Chris; Duchateau‐Nguyen, Guillemette; Johnson, Andrea; McLoughlin, P.; Navarro, Mercidita T.; Fleurbaey, C; Steiner, Lori; Tessier, Michel; Nguyen, Tracy; Wilhelm-Seiler, Monika; Caulfield, John P.

doi:10.1186/1755-8794-2-33

Cited by 31 publications

(36 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, progesterone treatment of murine peritoneal macrophages ex vivo enhanced the expression of MCP-1 and other cytokines following hydrogen peroxide exposure [21]. Differences in Kc/CXCL1 mRNA expression have also been reported among humans, where a study of whole blood from healthy volunteers found that women had a small but significant 1.3- to 1.5-fold increase in levels of Kc/CXCL1 mRNA compared to men [26]. The functional effects associated with higher mRNA levels may be limited in our study, however, as we did not observe significant differences between the genders for cytokine protein levels.…”

Section: Discussionmentioning

confidence: 85%

The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

et al. 2016

View full text Add to dashboard Cite

Inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice. GSH synthesis was impaired through genetic manipulation of Gclm, the modifier subunit of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis. Twenty-four hours after aspirating 25 µg of MWCNTs, all male mice developed neutrophilia in their lungs, regardless of Gclm genotype. However, female mice with moderate (Gclm heterozygous) and severe (Gclm null) GSH deficiencies developed significantly less neutrophilia. We found no indications of MWCNT-induced oxidative stress as reflected in the GSH content of lung tissue and epithelial lining fluid, 3-nitrotyrosine formation, or altered mRNA or protein expression of several redox-responsive enzymes. Our results indicate that GSH-deficient female mice are rendered uniquely susceptible to an attenuated neutrophil response. If the same effects occur in humans, GSH-deficient women manufacturing MWCNTs may be at greater risk for impaired neutrophil-dependent clearance of MWCNTs from the lung. In contrast, men may have effective neutrophil-dependent clearance, but may be at risk for lung neutrophilia regardless of their GSH levels.

show abstract

Section: Discussionmentioning

confidence: 85%

The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…For this reason, we investigated further whether sexual dimorphism in MS was driven by sex-specific genes. Sexrelated gene expression differences are normally present in several tissues, including blood [28,29], but they have never been specifically monitored under disease. Using relaxed statistics to maximize the number of differences existing in blood between genders, about 10% of the filtered genes resulted sex-specific in the healthy population, while only 2% in MS subjects.…”

Section: Sexual Dimorphism In Msmentioning

confidence: 99%

Gender-based blood transcriptomes and interactomes in multiple sclerosis: Involvement of SP1 dependent gene transcription

Menon

Dario

Cordiglieri

et al. 2012

Journal of Autoimmunity

View full text Add to dashboard Cite

“…This is the first evidence to suggest time-point and extraction variability in miR expression. Other transcriptomics studies have also found differences in RNA expression over the course of 1-day to several weeks (7,8) while longer time-points were inconclusive due to confounding of technical variability (10,11). …”

Section: Resultsmentioning

confidence: 99%

“…Several transcriptomic studies have shown limited fluctuation in blood RNAs when measured from healthy individuals over several weeks to months (7–11). The proportion of transcripts with high intra-individual variability was attributed to a small number of immunological genes (i.e., immunoglobulin) (9) or inseparable from technical variability due to poor experimental design (10,11). This evidence from transcriptomics suggests that there may be similarly small intra-individual variability for miR transcription, however, this has not been previously measured.…”

Section: Introductionmentioning

confidence: 99%

Improving Power to Detect Changes in Blood miRNA Expression by Accounting for Sources of Variability in Experimental Designs

Daniels

Sillé

Goldbaum

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background Blood microRNAs (miRs) are a new promising area of disease research, but variability in miR measurements may limit detection of true-positive findings. Here, we measured sources of miR variability and determine whether repeated measures can improve power to detect fold-change differences between comparison groups. Methods Blood from healthy volunteers (N=12) was collected at three time points. The miRs were extracted by a method predetermined to give the highest miR-yield. Nine different miRs were quantified using different qPCR assays and analyzed using mixed models to identify sources of variability. A larger number of miRs from a publicly-available blood miR microarray dataset with repeated measures was used for a bootstrapping procedure to investigate effects of repeated-measures on power to detect fold-changes in miR expression for a theoretical case-control study. Results Technical variability in qPCR replicates was identified as a significant source of variability (p<0.05) for all nine miRs tested. Variability was larger in the TaqMan qPCR assays (SD = 0.15–0.61) versus the qScript qPCR assays (SD = 0.08–0.14). Inter- and intra- individual and extraction variability also contributed significantly for two miRs. The bootstrapping procedure demonstrated that repeated measures (20–50% of N) increased detection of a 2-fold change for ~10–45% more miRs. Conclusion Statistical power to detect small-fold changes in blood miRs can be improved by accounting for sources of variability using repeated measures and choosing appropriate methods to minimize variability in miR quantification. Impact This study demonstrates the importance of including repeated measures in experimental designs for blood miR research.

show abstract

A longitudinal study of gene expression in healthy individuals

Cited by 31 publications

References 47 publications

The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

Gender-based blood transcriptomes and interactomes in multiple sclerosis: Involvement of SP1 dependent gene transcription

Improving Power to Detect Changes in Blood miRNA Expression by Accounting for Sources of Variability in Experimental Designs

Contact Info

Product

Resources

About