Genetic Associations and Differential mRNA Expression Levels of Host Genes Suggest a Viral Trigger for Endemic Pemphigus Foliaceus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient and Control Samples
2.1.1. Samples Used for the Association Analysis
2.1.2. Samples Used for RNA Expression Analysis
2.2. Selection of Candidate Genes
2.3. Genoty**
2.4. RNA-seq
2.5. Statistical Analysis
2.6. In Silico Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Endemic Pemphigus Foliaceus | Sporadic Pemphigus Foliaceus | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
GENE | SNP | MAF (%) | MODEL | CTR | PAT | OR | 95% CI | p | MAF (%) | MODEL | CTR | PAT | OR | 95% CI | p | ||
CTR | PAT | CTR | PAT | ||||||||||||||
TRIM5 | rs4992800 | 7.25 | 14.64 | add | 28/360 | 65/379 | 2.21 | [1.37–3.56] | 0.0012 | 2.40 | 3.33 | add | 7/285 | 5/145 | 1.34 | [0.45–4.0] | 0.5941 |
11p15.4 | a > C | rec | 1/193 | 5/217 | 4.53 | [0.52–39.17] | 0.17 | rec | 1/145 | 0/75 | NA | NA | NA | ||||
Intron 1 | dom | 27/167 | 60/162 | 2.30 | [1.38–3.86] | 0.0014 | dom | 6/140 | 5/70 | 1.67 | [0.49–5.65] | 0.4122 | |||||
USP15 | rs10160955 | 22.16 | 13.66 | add | 86/302 | 62/392 | 0.56 | [0.39–0.81] | 0.0017 | 15.69 | 25.33 | add | 43/231 | 38/112 | 1.74 | [1.07–2.79] | 0.0234 |
12q14.1 | T > c | rec | 12/182 | 4/223 | 0.27 | [0.08–0.84] | 0.0246 | rec | 8/129 | 3/72 | 0.67 | [0.17–2.61] | 0.566 | ||||
Intron 20 | dom | 74/120 | 58/169 | 0.17 | [0.00–17.43] | 0.4496 | dom | 35/102 | 35/40 | 2.55 | [1.40–4.62] | 0.0020 | |||||
NUP37 | rs11111162 | 19.37 | 26.89 | add | 74/308 | 121/329 | 1.44 | [1.03–2.00] | 0.0292 | 23.08 | 19.33 | add | 66/220 | 29/121 | 0.80 | [0.49–1.30] | 0.3671 |
12q23.2 | A > g | rec | 4/187 | 22/203 | 4.80 | [1.62–14.3] | 0.0047 | rec | 7/136 | 3/72 | 0.81 | [0.20–3.22] | 0.7645 | ||||
Intron 4 | dom | 70/121 | 99/126 | 1.28 | [0.86–1.91] | 0.2257 | dom | 59/84 | 26/49 | 0.75 | [0.42–1.35] | 0.3437 | |||||
NUP50 | rs2138156 | 30.67 | 41.85 | add | 119/269 | 190/264 | 1.56 | [1.18–2.07] | 0.0018 | 30.14 | 38.00 | add | 88/204 | 57/93 | 1.40 | [0.93–2.10] | 0.1047 |
22q13.31 | C > t | rec | 19/175 | 45/182 | 2.29 | [1.28–4.07] | 0.0049 | rec | 13/133 | 13/62 | 2.14 | [0.94–4.90] | 0.0700 | ||||
Intron 3 | dom | 100/94 | 145/82 | 1.62 | [1.09–2.41] | 0.0158 | dom | 75/71 | 44/31 | 1.34 | [0.76–2.36 | 0.3035 | |||||
NUP88 | rs1058398 | 45.36 | 38.55 | add | 176/212 | 175/279 | 0.72 | [0.54–0.96] | 0.0259 | - | - | - | - | - | - | - | - |
17p13.2 | A > g | rec | 33/161 | 36/191 | 0.87 | [0.52–1.48] | 0.0517 | - | - | - | - | - | - | ||||
3′UTR | dom | 143/51 | 139/88 | 0.54 | [0.35–0.83] | 0.0046 | - | - | - | - | - | - | |||||
TPR | rs3753565 | 4.40 | 9.47 | add | 17/369 | 43/411 | 2.43 | [1.35–4.4] | 0.0031 | 13.1 | 15.33 | add | 38/252 | 23/127 | 1.17 | [0.70–1.98] | 0.5491 |
1q31.1 | G > a Ser > Asn | rec | 1/192 | 2/225 | 1.33 | [0.11–15.94] | 0.8216 | rec | 4/141 | 4/71 | 1.99 | [0.48–8.17] | 0.3419 | ||||
Exon 22 | dom | 16/177 | 41/186 | 2.68 | [1.44–4.99] | 0.0018 | dom | 34/111 | 19/56 | 1.11 | [0.58–2.11] | 0.7567 | |||||
EIF4E | rs6834230 | 6.96 | 3.56 | add | 27/361 | 16/434 | 0.37 | [0.18–0.73] | 0.0045 | 0 | 0 | add | NA | NA | NA | NA | NA |
4q23 | C > t | rec | 1/193 | 0/225 | - | - | - | rec | NA | NA | NA | NA | NA | ||||
Intron 1 | dom | 26/168 | 16/209 | 0.37 | [0.18–0.75] | 0.0057 | dom | NA | NA | NA | NA | NA | |||||
EIF4E3 | rs1447904 | 27.32 | 36.73 | add | 106/282 | 166/286 | 1.49 | [1.10–2.00] | 0.0094 | 26.41 | 35.33 | add | 75/209 | 53/97 | 1.51 | [0.99–2.32] | 0.0573 |
3p13 | T > c | rec | 17/177 | 29/197 | 1.40 | [0.73–2.66] | 0.308 | rec | 9/133 | 11/64 | 2.54 | [1.00–6.44] | 0.0495 | ||||
Intron 2 | dom | 89/105 | 137/89 | 1.76 | [1.19–2.60] | 0.0046 | dom | 66/76 | 42/33 | 1.47 | [0.83–2.57] | 0.183 | |||||
JAK1 | rs310199 | 41.75 | 49.12 | add | 162/266 | 231/223 | 1.39 | [1.05–1.83] | 0.0205 | 28.67 | 27.7 | add | 82/204 | 41/107 | 0.95 | [0.60–1.67] | 0.8229 |
1p31.3 | A > g | rec | 39/155 | 56/171 | 1.23 | [0.77–1.97] | 0.3881 | rec | 10/133 | 3/71 | 0.56 | [0.15–2.10] | 0.3929 | ||||
Intron 2 | dom | 123/71 | 175/52 | 1.86 | [1.21–2.86] | 0.0046 | dom | 39/155 | 56/171 | 1.04 | [0.59–1.82] | 0.8887 | |||||
rs310202 | 30.05 | 39.6 | add | 116/270 | 179/273 | 1.48 | [1.10–2.0] | 0.0102 | 20.63 | 20.67 | add | 59/227 | 31/119 | 1.00 | [0.60–1.67] | 0.9923 | |
A > g | rec | 19/174 | 31/195 | 1.35 | [0.73–2.50] | 0.3382 | rec | 4/139 | 2/73 | 0.95 | [0.17–5.32] | 0.9554 | |||||
Intron 2 | dom | 97/96 | 148/78 | 1.781 | [1.20–2.65] | 0.0045 | dom | 55/88 | 29/46 | 1.00 | [0.57–1.79] | 0.9764 | |||||
TPCN2 | rs4930263 | 2.85 | 8.62 | add | 11/375 | 39/413 | 2.76 | [1.41–5.40] | 0.0031 | 0 | 0.68 | add | 0/276 | 1/145 | NA | NA | NA |
11q13.3 | a > C | rec | 1/192 | 4/222 | 3.01 | [0.33–27.5] | 0.328 | rec | 0/138 | 0/73 | NA | NA | NA | ||||
Intron 16 | dom | 10/183 | 35/191 | 3.20 | [1.53–6.69] | 0.0019 | dom | 0/138 | 1/72 | NA | NA | NA | |||||
IRF8 | rs1044873 | 42.27 | 36.5 | add | 164/224 | 165/287 | 0.76 | [0.57–1.02] | 0.0644 | 41.9 | 38.5 | add | 119/165 | 57/91 | 0.87 | [0.58–1.30] | 0.5014 |
16q24.1 | C > t | rec | 39/155 | 23/203 | 0.42 | [0.24–0.73] | 0.0024 | rec | 26/116 | 11/63 | 0.78 | [0.33–0.68] | 0.5243 | ||||
3′ UTR | dom | 125/69 | 142/84 | 0.93 | [0.62–1.39] | 0.7186 | dom | 93/49 | 46/28 | 0.87 | [0.48–1.55] | 0.6278 |
Genes | p | Fold Change |
---|---|---|
CCL5 | 3.885 × 10−06 | 1.4362 |
P4HB | 3.730 × 10−05 | 0.4185 |
APOBEC3G | 4.212 × 10−05 | 0.5244 |
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Hoch, V.B.-B.; Kohler, A.F.; Augusto, D.G.; Lobo-Alves, S.C.; Malheiros, D.; Cipolla, G.A.; Boldt, A.B.W.; Braun-Prado, K.; Wittig, M.; Franke, A.; et al. Genetic Associations and Differential mRNA Expression Levels of Host Genes Suggest a Viral Trigger for Endemic Pemphigus Foliaceus. Viruses 2022, 14, 879. https://doi.org/10.3390/v14050879
Hoch VB-B, Kohler AF, Augusto DG, Lobo-Alves SC, Malheiros D, Cipolla GA, Boldt ABW, Braun-Prado K, Wittig M, Franke A, et al. Genetic Associations and Differential mRNA Expression Levels of Host Genes Suggest a Viral Trigger for Endemic Pemphigus Foliaceus. Viruses. 2022; 14(5):879. https://doi.org/10.3390/v14050879
Chicago/Turabian StyleHoch, Valéria Bumiller-Bini, Ana Flávia Kohler, Danillo G. Augusto, Sara Cristina Lobo-Alves, Danielle Malheiros, Gabriel Adelman Cipolla, Angelica Beate Winter Boldt, Karin Braun-Prado, Michael Wittig, Andre Franke, and et al. 2022. "Genetic Associations and Differential mRNA Expression Levels of Host Genes Suggest a Viral Trigger for Endemic Pemphigus Foliaceus" Viruses 14, no. 5: 879. https://doi.org/10.3390/v14050879