An Exploratory Gene Expression Study of the Intestinal Mucosa of Patients with Non-Celiac Wheat Sensitivity
Abstract
:1. Introduction
2. Results
2.1. The Intestinal Mucosa of NCWS Patients Showed a Gene Expression Pattern Different from Controls
2.2. Gene Expression can Contribute to Identify the NCWS Status
2.3. Possible Pathological Mechanisms Engaged in NCWS
3. Discussion
4. Material and Methods
4.1. Patient’s Recruitment
4.2. RNA Isolation and Microarray Analysis
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Ethics Approval and Consent to Participate
Funding
Conflicts of Interest
Abbreviations
ATI | amylase trypsin inhibitor |
AUC | area under the curve |
DE | differentially expressed |
FDR | false discovery rate |
FODMAPs | fermentable oligo-, di-, monosaccharides |
HLA | human leukocyte antigen |
IBS | irritable bowel syndrome |
IPA | ingenuity pathway analysis |
LASSO | least absolute shrinkage and selection operator |
lncRNA | long non-coding RNA |
LPS | lipopolysaccharide |
NCWS | non-celiac wheat sensitivity |
PCA | principal component analysis |
SIBO | small intestinal bacterial overgrowth |
References
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Variables | CTRL | NCWS | p-Value a |
---|---|---|---|
Number of subjects | 7 | 12 | |
Age (years), mean ± SD | 56.3 ± 22.8 | 46.5 ± 11.7 | 0.228 |
Gender (M/F) | 1/6 | 0/12 | 0.779 b |
Marsh classification, n (%) | - | ||
0 | 6 (50.0) | ||
1 | 6 (50.0) | ||
3a | - | ||
3b | - | ||
3c | - | ||
TGA-IgA, (U/mL), mean ± SD | 1.8 ± 1.2 | 2.5 ± 1.6 | 0.331 |
Hp positive, n (%) | 4 (57.1) | 2 (16.7) | 0.187 b |
HLA-DQ, n (%) | 0.767 b | ||
Negative | 5 (71.4) | 8 (66.7) | |
DQ2 | 2 (28.6) | 4 (33.3) | |
EMA positive | - | - | - |
ESR (mm/h), mean ± SD | 12.6 ± 4.3 | 14.3 ± 4.7 | 0.444 |
CRP (mg/L), mean ± SD | 0.4 ± 0.2 | 0.4 ± 0.3 | 0.998 |
Calprotectin (µg/g), mean ± SD | 68.0 ± 35.5 | 85.3 ± 79.9 | 0.598 |
Hb (g/dL), mean ± SD | 12.7 ± 0.8 | 13.0 ± 0.7 | 0.404 |
Ferritin (ng/mL), mean ± SD | 24.2 ± 20.2 | 22.3 ± 16.7 | 0.827 |
BMI (kg/m2), mean ± SD | 25.8 ± 4.0 | 27.6 ± 4.1 | 0.365 |
Number of Transcripts Analysed | % | Absolute Mean Difference > 1 | % | Benjamini–Hochberg Correction p-Value < 0.05 | % | |
---|---|---|---|---|---|---|
Total | 53,217 | 100 | 429 | 100 | 300 | 100 |
Protein-coding | 27,883 | 52.4 | 188 | 43.8 | 110 | 36.7 |
Non-coding | 25,334 | 47.6 | 241 | 56.2 | 190 | 63.3 |
Xloc or Loc | 4769 | 18.8 | 42 | 17.4 | 30 | 15. 8 |
LNC | 9200 | 36.3 | 84 | 34.9 | 65 | 34.2 |
Linc | 1419 | 5.6 | 17 | 7.1 | 17 | 8.9 |
-AS | 1465 | 5.8 | 13 | 5.4 | 11 | 5.8 |
SNORA- | 118 | 0.46 | 1 | 0.4 | 1 | 0.5 |
SNORD- | 185 | 0.73 | 2 | 0.8 | 2 | 1.1 |
-IT | 63 | 0.24 | 1 | 0.4 | 1 | 0.5 |
No name | 8115 | 32.0 | 81 | 33.6 | 63 | 33.2 |
Probe Name | Gene Symbol | Variable Importance | AUC (95% CI) |
---|---|---|---|
A_22_P00006238 | N/A | −2.299 | 0.990 (0.958–1.000) |
A_21_P0011074 | XLOC_l2_003253 | 1.795 | 0.969 (0.901–1.000) |
A_21_P0005811 | lnc-DUSP4-2 | 1.413 | 0.939 (0.838–1.000) |
A_22_P00022828 | lnc-RLBP1-1 | −0.480 | 0.923 (0.806–1.000) |
A_21_P0011522 | XLOC_l2_005692 | 0.506 | 0.908 (0.784–1.000) |
A_23_P27207 | SfigureCGB1C1 | −0.028 | 0.908 (0.773–1.000) |
A_33_P3389286 | SFN | 0.263 | 0.913 (0.779–1.000) |
A_24_P36229 | DTNA | −0.105 | 0.893 (0.755–1.000) |
A_21_P0001949 | LOC101927431 | 0.881 | 0.867 (0.643–1.000) |
A_33_P3266564 | KRTAP5-6 | 0.644 | 0.857 (0.689–1.000) |
A_21_P0008666 | lnc-SH3GL3-1 | −0.173 | 0.827 (0.568–1.000) |
A_24_P263284 | CSMD2 | −0.325 | 0.770 (0.543–0.998) |
A_24_P281395 | N/A | −0.006 | 0.755 (0.462–1.000) |
A_21_P0007206 | lnc-CTD-2210P24.4.1-3 | 0.226 | 0.745 (0.478–1.000) |
A_22_P00001191 | lnc-ANGPTL2-3 | −0.121 | 0.684 (0.391–0.977) |
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Efthymakis, K.; Clemente, E.; Marchioni, M.; Di Nicola, M.; Neri, M.; Sallese, M. An Exploratory Gene Expression Study of the Intestinal Mucosa of Patients with Non-Celiac Wheat Sensitivity. Int. J. Mol. Sci. 2020, 21, 1969. https://doi.org/10.3390/ijms21061969
Efthymakis K, Clemente E, Marchioni M, Di Nicola M, Neri M, Sallese M. An Exploratory Gene Expression Study of the Intestinal Mucosa of Patients with Non-Celiac Wheat Sensitivity. International Journal of Molecular Sciences. 2020; 21(6):1969. https://doi.org/10.3390/ijms21061969
Chicago/Turabian StyleEfthymakis, Konstantinos, Emanuela Clemente, Michele Marchioni, Marta Di Nicola, Matteo Neri, and Michele Sallese. 2020. "An Exploratory Gene Expression Study of the Intestinal Mucosa of Patients with Non-Celiac Wheat Sensitivity" International Journal of Molecular Sciences 21, no. 6: 1969. https://doi.org/10.3390/ijms21061969