The Isoform GC1f of the Vitamin D Binding Protein Is Associated with Bronchiectasis Severity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Study Procedures
2.3. GC Single Nucleotide Polymorphisms (SNPs) Genotyping
2.4. Clinical Evaluation
2.5. Statistical Analysis
3. Results
3.1. GC Isoforms and Clinical Characteristics
3.1.1. GC1f Isoform
3.1.2. GC1s Isoform
3.1.3. GC2 Isoform
3.2. GC Isoform Phenotypes and Clinical Characteristics
4. Discussion
Strength and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Isoform | GC rs7041 | GC rs4588 |
---|---|---|
GC1f | A | G |
GC1s | C | G |
GC2 | A | T |
Isoform | Genotype (rs7041/rs4588) | Bronchiectasis n (%) |
---|---|---|
GC1s | C/G | 95 (81.9)% |
GC1f | A/G | 37 (31.9)% |
GC2 | A/T | 55 (47.4)% |
Isoform Phenotype | Genotype (rs7041/rs4588) | Bronchiectasis n (%) |
GC1f-GC1f | A/G-A/G | 0 (0)% |
GC1s-GC1f | C/G-A/G | 24 (20.7)% |
GC1s-GC1s | C/G-C/G | 37 (31.9)% |
GC1s-GC2 | C/G-A/T | 34 (29.3)% |
GC1f-GC2 | A/G-A/T | 13 (11.2)% |
GC2-GC2 | A/T-A/T | 8 (6.9)% |
Demography | ||||
---|---|---|---|---|
GC1f (N = 37) | Other Isoforms (N = 79) | p-Value | ||
Sex (Female) | 26 (70.3%) | 52 (65.8%) | 0.634 | |
Age | 61.0 (53.0, 71.0) | 63.0 (48.0, 72.0) | 0.528 | |
BMI | 22.0 (19.0, 25.0) | 21.7 (19.0, 24.2) | 0.902 | |
Radiology | ||||
Reiff score | 4.0 (3.0, 6.0) | 4.0 (3.0, 4.5) | 0.615 | |
Disease Severity | ||||
BSI score | 7.0 (4.0, 10.0) | 6.0 (3.5, 9.0) | 0.318 | |
BSI risk classes | mild | 11 (29.7%) | 29 (36.7%) | 0.675 |
moderate | 12 (32.4%) | 26 (32.9%) | ||
severe | 14 (37.8%) | 24 (30.4%) | ||
BSI Moderate-severe | 26 (70.3%) | 50 (63.3%) | 0.461 | |
BSI Severe | 14 (37.8%) | 24 (30.4%) | 0.425 | |
FACED score | 2.0 (1.0, 4.0) | 2.0 (1.0, 4.0) | 0.669 | |
FACED risk classes | mild | 21 (56.8%) | 42 (53.2%) | 0.055 |
moderate | 9 (24.3%) | 32 (40.5%) | ||
severe | 7 (18.9%) | 5 (6.3%) | ||
FACED Moderate–severe | 16 (43.2%) | 37 (46.8%) | 0.717 | |
FACED Severe | 7 (18.9%) | 5 (6.3%) | 0.038 | |
Clinical Status | ||||
Exacerbation in the previous year | 2.0 (1.0, 3.0) | 2.0 (1.0, 3.0) | 0.887 | |
Hospitalization (at least one previous year) | 7 (19.4%) | 6 (7.6%) | 0.063 | |
Comorbidities | ||||
BACI | 0.0 (0.0, 3.0) | 0.0 (0.0, 3.0) | 0.505 | |
Osteoporosis | 2 (5.4%) | 6 (7.6%) | 0.664 | |
Depression | 2 (5.4%) | 10 (12.7%) | 0.232 | |
Anxiety | 1 (2.7%) | 4 (5.1%) | 0.56 | |
Asthma | 2 (5.4%) | 18 (22.8%) | 0.021 | |
Lung Function | ||||
FEV1% | 79.5 (69.8, 102.0) | 84.5 (69.2, 98.5) | 0.602 | |
FEV1% < 50% | 6 (16.7%) | 9 (11.5%) | 0.451 | |
FEV1% < 35% | 3 (8.3%) | 5 (6.4%) | 0.709 | |
Standard Microbiology | ||||
Chronic infection | 21 (57.6%) | 29 (36.7%) | 0.041 | |
Chronic P. aeruginosa | 12 (36.4%) | 18 (26.1%) | 0.287 | |
Chronic H. influenzae | 2 (6.1%) | 4 (5.8%) | 0.958 | |
Chronic MSSA | 4 (12.1%) | 4 (5.8%) | 0.266 | |
Chronic A. xylosoxidans | 1 (3.0%) | 1 (1.4%) | 0.59 | |
Chronic Others | 2 (2.9%) | 2 (6.1%) | 0.441 | |
Aetiology | ||||
Idiopathic | 17 (45.9%) | 46 (58.2%) | 0.477 | |
Primary Ciliary Dyskinesia | 5 (13.5%) | 5 (6.3%) | ||
Primary immunodeficiency | 4 (10.8%) | 9 (11.4%) | ||
Post Infective | 3 (8.1%) | 3 (3.8%) | ||
Secondary Immunodeficiency | 4 (10.8%) | 2 (2.5%) | ||
Others * | 4 (10.8%) | 14 (17.8%) | ||
QoL-B Questionnaire | ||||
Physical section | 66.7 (43.4, 86.7) | 60.0 (41.3, 80.0) | 0.459 | |
Role section | 70.0 (53.3, 93.3) | 66.7 (49.2, 86.7) | 0.502 | |
Vitality section | 61.2 (44.4, 77.8) | 55.6 (33.3, 66.7) | 0.232 | |
Emotion section | 83.3 (75.0, 100.0) | 75.0 (50.0, 85.4) | 0.019 | |
Social section | 75.0 (39.6, 91.7) | 58.3 (41.7, 83.3) | 0.452 | |
Treatment Burden section | 77.8 (58.4, 77.8) | 66.7 (55.6, 77.8) | 0.095 | |
Health section | 44.4 (33.3, 66.7) | 37.5 (16.7, 58.3) | 0.25 | |
Respiration section | 74.1 (66.7, 81.5) | 74.1 (58.3, 81.5) | 0.451 | |
Vitamin D | ||||
Vitamin D (ng/mL) | 20.2 (11.0, 26.0) | 20.4 (14.8, 29.1) | 0.224 |
Demography | ||||
---|---|---|---|---|
GC1s (N = 95) | Other Isoforms (N = 21) | p-Value | ||
Sex (Female) | 64 (67.4%) | 14 (66.7%) | 0.951 | |
Age | 62.0 (48.0, 72.0) | 62.0 (49.0, 71.0) | 0.991 | |
BMI | 21.6 (19.0, 24.2) | 22.0 (19.0, 26.0) | 0.397 | |
Radiology | ||||
Reiff score | 4.0 (3.0, 5.5) | 4.0 (3.0, 6.0) | 0.746 | |
Disease Severity | ||||
BSI score | 6.0 (3.5, 9.0) | 6.0 (4.0, 10.0) | 0.793 | |
BSI risk classes | mild | 33 (34.7%) | 7 (33.3%) | 0.993 |
moderate | 31 (32.6%) | 7 (33.3%) | ||
severe | 31 (32.6%) | 7 (33.3%) | ||
BSI Moderate-severe | 62 (65.3%) | 14 (66.7%) | 0.903 | |
BSI Severe | 31 (32.6%) | 7 (33.3%) | 0.951 | |
FACED score | 2.0 (1.0, 4.0) | 3.0 (2.0, 4.0) | 0.3 | |
FACED risk classes | mild | 53 (55.8%) | 10 (47.6%) | 0.722 |
moderate | 33 (34.7%) | 8 (38.1%) | ||
severe | 9 (9.5%) | 3 (14.3%) | ||
FACED Moderate-severe | 42 (44.2%) | 11 (52.4%) | 0.496 | |
FACED Severe | 9 (9.5%) | 3 (14.3%) | 0.512 | |
Clinical Status | ||||
Exacerbation in the previous year | 2.0 (1.0, 3.0) | 2.0 (1.0, 3.0) | 0.449 | |
Hospitalization (at least one previous year) | 11 (11.6%) | 2 (10.0%) | 0.839 | |
Comorbidities | ||||
BACI | 0.0 (0.0, 2.5) | 3.0 (0.0, 3.0) | 0.035 | |
Osteoporosis | 8 (8.4%) | 0 (0.0%) | 0.168 | |
Depression | 12 (12.6%) | 0 (0.0%) | 0.085 | |
Anxiety | 90 (94.7%) | 21 (100.0%) | 0.282 | |
Asthma | 15 (15.8%) | 5 (23.8%) | 0.379 | |
Lung Function | ||||
FEV1% | 84.0 (70.0, 101.0) | 83.0 (56.0, 88.0) | 0.233 | |
FEV1% < 50% | 11 (11.8%) | 4 (19.0%) | 0.377 | |
FEV1% < 35% | 5 (5.4%) | 3 (14.3%) | 0.149 | |
Standard Microbiology | ||||
Chronic infection | 41 (48.2%) | 9 (52.9%) | 0.723 | |
Chronic P. aeruginosa | 24 (28.2%) | 6 (35.3%) | 0.56 | |
Chronic H. influenzae | 6 (7.1%) | 0 (0.0%) | 0.259 | |
Chronic MSSA | 8 (9.4%) | 0 (0.0%) | 0.188 | |
Chronic A. xylosoxidans | 1 (1.2%) | 1 (5.9%) | 0.201 | |
Chronic Others | 3 (3.5%) | 1 (5.9%) | 0.648 | |
Aetiology | ||||
Idiopathic | 47 (49.5%) | 16 (76.2%) | 0.739 | |
Primary Ciliary Dyskinesia | 10 (10.5%) | 0 (0.0%) | ||
Primary Immunodeficiency | 9 (9.5%) | 4 (19.0%) | ||
Post Infective | 6 (6.3%) | 0 (0.0%) | ||
Secondary Immunodeficiency | 5 (5.3%) | 1 (4.8%) | ||
Others * | 18(18.9%) | 0 (0%) | ||
QoL-B Questionnaire | ||||
Physical section | 63.4 (41.3, 80.0) | 55.6 (40.0, 70.0) | 0.608 | |
Role section | 66.7 (53.3, 86.7) | 73.3 (56.6, 90.0) | 0.873 | |
Vitality section | 55.6 (33.3, 66.7) | 55.6 (44.4, 77.8) | 0.724 | |
Emotion section | 75.0 (56.2, 91.7) | 75.0 (62.5, 95.8) | 0.684 | |
Social section | 58.3 (41.7, 83.3) | 83.3 (62.5, 87.5) | 0.147 | |
Treatment Burden section | 66.7 (55.6, 77.8) | 66.7 (55.6, 77.8) | 0.855 | |
Health section | 37.5 (22.9, 58.3) | 44.4 (23.6, 58.4) | 0.995 | |
Respiration section | 74.1 (58.5, 82.8) | 74.1 (63.0, 77.8) | 0.478 | |
Vitamin D | ||||
Vitamin D (ng/mL) | 20.5 (14.3, 29.7) | 15.8 (7.6, 22.4) | 0.037 |
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Oriano, M.; Aliberti, S.; Guerini, F.R.; Agliardi, C.; Di Francesco, C.; Gelmini, A.; Terranova, L.; Zanzottera, M.; Marchisio, P.; Clerici, M.; et al. The Isoform GC1f of the Vitamin D Binding Protein Is Associated with Bronchiectasis Severity. Biomedicines 2021, 9, 1573. https://doi.org/10.3390/biomedicines9111573
Oriano M, Aliberti S, Guerini FR, Agliardi C, Di Francesco C, Gelmini A, Terranova L, Zanzottera M, Marchisio P, Clerici M, et al. The Isoform GC1f of the Vitamin D Binding Protein Is Associated with Bronchiectasis Severity. Biomedicines. 2021; 9(11):1573. https://doi.org/10.3390/biomedicines9111573
Chicago/Turabian StyleOriano, Martina, Stefano Aliberti, Franca Rosa Guerini, Cristina Agliardi, Carlotta Di Francesco, Alice Gelmini, Leonardo Terranova, Milena Zanzottera, Paola Marchisio, Mario Clerici, and et al. 2021. "The Isoform GC1f of the Vitamin D Binding Protein Is Associated with Bronchiectasis Severity" Biomedicines 9, no. 11: 1573. https://doi.org/10.3390/biomedicines9111573