Background
Methods
Study subjects
Clinical diagnoses
Data collection
m-WGS and analysis
SNaPshot analysis
qRT-PCR validation
Western blotting
Ethics statement
Statistical analysis
Results
Spectrum of mitochondrial genome variants
Variables | Total (n = 134) | Case (n = 68) | Control (n = 66) | p-value |
---|---|---|---|---|
Age, Mean (SD) | 36.72 (15.82) | 35.87 (13.92) | 37.59 (17.64) | 0.531 |
Sex, n (%) | 0.999 | |||
Male | 67 (50) | 34 (50) | 33 (50) | |
Female | 67 (50) | 34 (50) | 33 (50) | |
IgE, median (Q1,Q3) | 42.15 (16.75, 134.75) | 115 (41.15, 343) | 19.1 (8.17, 45.07) | < 0.001 |
Family history, n (%) | < 0.001 | |||
No | 113 (84.33) | 47 (69.12) | 66 (100) | |
Yes | 21 (15.67) | 21 (30.88) | 0 (0) | |
Drug allergy, n (%) | < 0.001 | |||
No | 121 (90.3) | 55 (80.88) | 66 (100) | |
Yes | 13 (9.7) | 13 (19.12) | 0 (0) |
Association of mitochondrial variants with AR
SNP NO | Gene | Region | Rare Allele | FA | FC | OR (95%CI) | p-value | pBH | pB |
---|---|---|---|---|---|---|---|---|---|
MT4715.A/G | ND2 | Synonymous | G | 4/132 | 24/108 | 0.1332(0.04467–0.3973) | 0.0003 | 0.0276 | 0.0276 |
MT15487.A/T | CYTB | Synonymous | T | 4/132 | 22/110 | 0.1494(0.04983–0.4477) | 0.000687 | 0.0316 | 0.0632 |
MT7196.C/A | COX1 | Synonymous | A | 4/132 | 22/110 | 0.1494(0.04983–0.4477) | 0.000687 | 0.0211 | 0.0632 |
MT302.-/CCC | NONE | Intergenic | CCC | 34/102 | 14/118 | 2.795(1.417–5.516) | 0.003037 | 0.0699 | 0.2794 |
MT6962.G/A | COX1 | Synonymous | A | 18/118 | 4/128 | 5.071(1.652–15.56) | 0.004547 | 0.0837 | 0.4183 |
MT10609.T/C | ND4L | Nonsynonymous | C | 16/120 | 4/128 | 4.5(1.442–14.04) | 0.009597 | 0.1472 | 0.8829 |
MT12406.G/A | ND5 | Nonsynonymous | A | 16/120 | 4/128 | 4.5(1.442–14.04) | 0.009597 | 0.1261 | 0.8829 |
MT12882.C/T | ND5 | Synonymous | T | 16/120 | 4/128 | 4.5(1.442–14.04) | 0.009597 | 0.1104 | 0.8829 |
MT16298.T/C | tRNA-Pro | Intergenic | C | 8/128 | 20/112 | 0.3442(0.1457–0.8133) | 0.01506 | 0.1111 | 1.0000 |
MT13759.G/A | ND5 | Nonsynonymous | A | 12/124 | 2/130 | 6.684(1.445–30.92) | 0.01507 | 0.1000 | 1.0000 |
MT16311.T/C | tRNA-Pro | Intergenic | C | 26/110 | 12/120 | 2.478(1.178–5.213) | 0.01682 | 0.0909 | 1.0000 |
MT8584.G/A | ATP6 | Nonsynonymous | A | 14/122 | 26/106 | 0.4546(0.225–0.9186) | 0.02805 | 0.0833 | 1.0000 |
MT14668.C/T | ND6 | Synonymous | T | 34/102 | 20/112 | 1.925(1.033–3.587) | 0.03914 | 0.0769 | 1.0000 |
MT8414.C/T | ATP8 | Nonsynonymous | T | 34/102 | 20/112 | 1.925(1.033–3.587) | 0.03914 | 0.0714 | 1.0000 |
MT16260.C/T | tRNA-Pro | Intergenic | T | 4/132 | 12/120 | 0.2953(0.09186–0.949) | 0.04058 | 0.0667 | 1.0000 |
MT10310.G/A | ND3 | Synonymous | A | 18/118 | 8/124 | 2.461(1.015–5.964) | 0.04618 | 0.0625 | 1.0000 |
MT6392.T/C | COX1 | Synonymous | C | 18/118 | 8/124 | 2.461(1.015–5.964) | 0.04618 | 0.0588 | 1.0000 |
Independent cohort validation for mtSNPs
Variables | Total (n = 120) | Case (n = 69) | Control (n = 51) | p-value |
---|---|---|---|---|
Age, median (Q1,Q3) | 33 (24, 46) | 35 (24, 46) | 31 (22, 46) | 0.294 |
Sex, n (%) | 0.860 | |||
Male | 67 (56%) | 39 (57%) | 28 (55%) | |
Female | 53 (44%) | 30 (43%) | 23 (45%) | |
IgE, median (Q1,Q3) | 53 (16, 190) | 148 (45, 299) | 16 (8, 29) | < 0.001 |
Family history, n (%) | < 0.001 | |||
No | 81 (68%) | 30 (43%) | 51 (100%) | |
Yes | 39 (32%) | 39 (57%) | 0 (0%) | |
Drug allergy, n (%) | 0.003 | |||
No | 98 (82%) | 51 (74%) | 47 (92.16%) | |
Yes | 21 (18%) | 18 (26%) | 4 (7.84%) |
SNP NO | Gene | Genotype | Case | Control | χ2 | OR (95%CI) | p-value |
---|---|---|---|---|---|---|---|
rs148377232 (MT16298.T/C) | tRNA-Pro | C | 8 | 10 | 1.722 | 0.512(0.186–1.408) | 0.190 |
T | 61 | 39 | |||||
rs1970771 (MT6962.G/A) | COX1 | A | 12 | 9 | 0.001 | 0.983(0.379–2.545) | 0.971 |
G | 57 | 42 | |||||
rs200487531 (MT10609.T/C) | ND4L | C | 12 | 9 | 0.007 | 0.959(0.370–2.487) | 0.932 |
T | 57 | 41 | |||||
rs28357370 (MT15487.A/T) | CYTB | T | 7 | 7 | 0.365 | 0.710(0.232–2.168) | 0.546 |
A | 62 | 44 | |||||
rs28357678 (MT14668.C/T) | ND6 | T | 12 | 5 | 1.464 | 1.971(0.647–6.005) | 0.226 |
C | 56 | 46 | |||||
rs28357976 (MT4715.A/G) | ND2 | G | 7 | 7 | 0.415 | 0.694(0.227–2.120) | 0.519 |
A | 62 | 43 | |||||
rs28358875 (MT7196.C/A) | COX1 | A | 7 | 7 | 0.365 | 0.710(0.232–2.168) | 0.546 |
C | 62 | 44 | |||||
rs28358884 (MT8414.C/T) | ATP8 | T | 12 | 5 | 1.388 | 1.937(0.636–5.896) | 0.239 |
C | 57 | 46 | |||||
G | 51 | 39 | |||||
rs28617389 (MT12406.G/A) | ND5 | A | 14 | 9 | 0.132 | 1.188(0.469–3.007) | 0.716 |
G | 55 | 42 | |||||
T | 48 | 32 | |||||
rs3135028 (MT8584.G/A) | ATP6 | A | 8 | 14 | 4.925 | 0.347(0.133–0.905) | 0.027 |
G | 61 | 37 | |||||
rs34799580 (MT16311.T/C) | tRNA-Pro | C | 10 | 7 | 0.030 | 1.084(0.382–3.073) | 0.880 |
T | 58 | 44 | |||||
G | 69 | 48 | |||||
rs373855397 (MT16260.C/T) | tRNA-Pro | T | 3 | 2 | 0.013 | 1.114(0.179–6.921) | 0.908 |
C | 66 | 49 | |||||
rs376513041 (MT6392.T/C) | COX1 | G | 15 | 12 | 0.036 | 0.920(0.388–2.183) | 0.850 |
T | 53 | 39 | |||||
C | 69 | 48 | |||||
A | 65 | 47 | |||||
rs386420001 (MT12882.C/T) | ND5 | T | 12 | 9 | 0.001 | 0.983(0.379–2.545) | 0.980 |
C | 57 | 42 | |||||
G | 63 | 46 | |||||
rs386420024 (MT13759.G/A) | ND5 | A | 11 | 7 | 0.136 | 1.213(0.435–3.384) | 0.712 |
G | 57 | 44 | |||||
A | 68 | 48 | |||||
rs41467651 (MT10310.G/A) | ND3 | T | 15 | 12 | 0.084 | 0.880(0.370–2.089) | 0.771 |
G | 54 | 38 |