Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure
Abstract
:1. Introduction
2. Subjects and Methods
2.1. Study Population
2.2. DNA Isolation
2.3. Genetic Variations Selection for this Study
2.4. Genotype Analysis
2.5. Statistical Analysis
3. Results
3.1. Clinical Characteristics of ARF Study Group
3.2. SNP–SNP Interaction
3.3. Association of SP Genes SNPs with ARF Compared to Newborn Controls after Adjusting for Sex and Ethnicity
3.4. Haplotype Association with ARF Risk
3.5. Association of SP Genes with the PDAD Subgroup Compared to no PDAD after Individual Adjustments of Variables
3.5.1. Age
3.5.2. Positive Bacterial Culture
3.5.3. Ventilator Days
3.6. Common SNP–SNP Interactions
3.6.1. Association with ARF Compared to Controls and PDAD Compared to No PDAD
3.6.2. Associations with PDAD Compared to No PDAD after Adjusting for Age, Positive Bacterial Culture, and Ventilator Days
4. Discussion
4.1. Association of SFTPC with ARF in a Single-SNP Model
4.2. Association of Interactions of SNPs of SP Genes with ARF and PDAD
4.3. Association of SNPs of SFTPA2 with ARF
4.4. Association of SNPs of SFTPA1 with PDAD
4.5. Association of SFTPD with Decreased Risk of PDAD
4.6. Interactions of Hydrophobic SPs (SFTPB and SFTPC) with ARF and PDAD
4.7. Haplotype Association with ARF Risk
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | No PDAD (n = 162) | PDAD (n = 86) | p value |
---|---|---|---|
Demographics Age (months) Female/male (%/%) | 2.8 ± 3.5 63/99 (39/61) | 5.4 ± 5.6 36/50 (42/58) | <0.001 0.89 |
Race White Black Mixed/Other | 129 (80) 23 (14) 10 (6) | 66 (77) 15 (17) 5 (6) | 0.74 |
Ethnicity Hispanic Non-Hispanic | 31 (19) 131 (81) | 21 (24) 65 (76) | 0.61 |
Admission diagnosis (%) RSV bronchiolitis Other bronchiolitis Other pneumonia Other respiratory failure Non-pulmonary | 89 (55) 39 (24) 13 (8) 17 (10) 4 (2) | 38 (44) 17 (20) 17 (20) 12 (14) 2 (2) | 0.08 |
PRISM III score | 4.6 ± 3.6 | 4.8 ± 4.0 | 0.69 |
Specific virus (%) (n = 187) RSV Influenza Parainfluenza Adenovirus | 102 (79) 3 (2) 1 (1) 1 (1) | 38 (64) 1 (1) 2 (2) 2 (3) | 0.03 1 0.33 0.24 |
Positive bacterial culture (%)(n = 195) | 81 (63) | 54 (82) | 0.009 |
Duration of support Ventilator days Oxygen days PICU days | 6.5 ± 4.0 10.0 ± 5.1 8.3 ± 4.6 | 9.5 ± 12.1 12.7 ± 14.5 12.1 ± 13.5 | 0.004 0.03 0.001 |
Gene | SNP #1 ID | Gene | SNP #2 ID | Gene | SNP #3 ID | Interaction | p value | FDR | OR (95% CI) | |
---|---|---|---|---|---|---|---|---|---|---|
One dominant effect | ||||||||||
1 * | SFTPA2 | rs1059046 | SFTPA2 | rs1965707 | SFTPA1 | rs1059047 | a1 × d2 × a3 | 0.001285994 | 0.001 | 2.2 (1.3–3.6) |
2 * | SFTPA2 | rs1059046 | SFTPA2 | rs1965707 | SFTPA1 | rs1136451 | 0.001052925 | 0.00105 | 2.2 (1.3–3.7) | |
3 * | SFTPA2 | rs1059046 | SFTPA2 | rs1965707 | SFTPA1 | rs4253527 | 0.000833915 | 0.00083 | 2.3 (1.4–4.0) | |
4 * | SFTPA2 | rs1059046 | SFTPA2 | rs1965708 | SFTPA1 | rs1136451 | 0.000662744 | 0.00066 | 2.6 (1.4–4.7) | |
5 #a | SFTPA2 | rs1059046 | SFTPA2 | rs17886395 | SFTPA2 | rs1965708 | a1 × a2 × d3 | 0.000229167 | 0.00020 | 0.4 (0.2–0.7) |
Two dominant effect | ||||||||||
1 *a | SFTPA2 | rs1059046 | SFTPA2 | rs17886395 | SFTPA2 | rs1965707 | a1 × d2 × d3 | 0.00008108 | 0.00008 | 2.1 (1.4–3.2) |
2 *a | SFTPA2 | rs1059046 | SFTPA2 | rs17886395 | SFTPA2 | rs1965708 | 0.001549286 | 0.00155 | 1.8 (1.2–2.7) | |
3 * | SFTPA2 | rs1059046 | SFTPA2 | rs1965707 | SFTPA1 | rs1059047 | 0.00341059 | 0.00341 | 1.8 (1.2–2.7) | |
4 * | SFTPA2 | rs1059046 | SFTPA2 | rs1965707 | SFTPA1 | rs1136451 | 0.002675982 | 0.00268 | 1.8 (1.2–2.7) | |
5 * | SFTPA2 | rs1059046 | SFTPA2 | rs1965708 | SFTPA1 | rs1059047 | 0.000228776 | 0.00023 | 2.2 (1.4–3.5) | |
6 * | SFTPA2 | rs1059046 | SFTPA1 | rs1059047 | SFTPA1 | rs1136450 | 0.001111869 | 0.00111 | 2.1 (1.3–3.3) | |
7 # | SFTPA2 | rs1965707 | SFTPA2 | rs1965708 | SFTPC | rs4715 | 0.00053651 | 0.00050 | 0.3 (0.1–0.6) | |
8 #a | SFTPA1 | rs1059047 | SFTPA1 | rs1136451 | SFTPA1 | rs4253527 | 0.004439716 | 0.00400 | 0.3 (0.1–0.8) | |
9 *a | SFTPA2 | rs1059046 | SFTPA2 | rs17886395 | SFTPA2 | rs1965707 | d1 × a2 × d3 | 0.000424175 | 0.00042 | 1.8 (1.3–2.5) |
10 *a | SFTPA2 | rs1059046 | SFTPA2 | rs17886395 | SFTPA2 | rs1965708 | 0.001836416 | 0.00184 | 1.7 (1.2–2.3) | |
11 * | SFTPA2 | rs17886395 | SFTPA1 | rs1136450 | SFTPC | rs4715 | 0.000648071 | 0.00049 | 4.0 (1.7–10.1) | |
12 # | SFTPA2 | rs17886395 | SFTPA1 | rs1059047 | SFTPA1 | rs1136450 | 0.000490381 | 0.00060 | 0.6 (0.5–0.8) | |
13 * | SFTPA2 | rs17886395 | SFTPA2 | rs1965707 | SFTPA1 | rs1136450 | d1 × d2 × a3 | 0.000191969 | 0.00019 | 2.2 (1.4–3.4) |
14 # | SFTPA2 | rs17886395 | SFTPA1 | rs1136450 | SFTPC | rs4715 | 0.000158449 | 0.00010 | 0.2 (0.1–0.5) | |
Three dominant effect | ||||||||||
1 * | SFTPA2 | rs17886395 | SFTPA1 | rs1136451 | SFTPA1 | rs4253527 | d1 × d2 × d3 | 0.000333494 | 0.00005 | 1.6 (1.3–2.1) |
2 #a | SFTPA2 | rs1059046 | SFTPA2 | rs17886395 | SFTPA2 | rs1965708 | 0.005639344 | 0.00030 | 0.6 (0.5–0.8) | |
3 # | SFTPA2 | rs1059046 | SFTPA2 | rs1965707 | SFTPC | rs4715 | 0.004814545 | 0.00600 | 0.6 (0.4–0.9) | |
4 # | SFTPA2 | rs1059046 | SFTPA1 | rs1059047 | SFTPA1 | rs1136450 | 0.00000000002 | 0.00500 | 0.7 (0.6–0.9) | |
5 # | SFTPA2 | rs1059046 | SFTPA1 | rs1136450 | SFTPC | rs4715 | 0.00336572 | 0.00000 | 0.3 (0.2–0.4) | |
6 # | SFTPA2 | rs1059046 | SFTPA1 | rs1136451 | SFTPC | rs4715 | 0.000000227 | 0.00300 | 0.5 (0.4–0.8) | |
7 #a | SFTPA2 | rs17886395 | SFTPA2 | rs1965707 | SFTPA2 | rs1965708 | 0.000004297 | 0.00000 | 0.5 (0.4–0.7) | |
8 # | SFTPA2 | rs17886395 | SFTPA1 | rs1059047 | SFTPA1 | rs1136450 | 0.000809901 | 0.00000 | 0.6 (0.5–0.7) | |
9 # | SFTPA2 | rs17886395 | SFTPA1 | rs1059047 | SFTPA1 | rs1136451 | 0.000054837 | 0.00080 | 0.7 (0.5–0.9) | |
10 # | SFTPA2 | rs17886395 | SFTPA1 | rs1136451 | SFTPC | rs4715 | 0.000094992 | 0.00009 | 0.4 (0.3–0.7) | |
11 # | SFTPA2 | rs17886395 | SFTPA1 | rs4253527 | SFTPC | rs4715 | 0.00329539 | 0.00300 | 0.5 (0.3–0.8) | |
12 # | SFTPA2 | rs1965707 | SFTPA2 | rs1965708 | SFTPA1 | rs1136450 | 0.000141004 | 0.00010 | 0.7 (0.5–0.8) | |
13 # | SFTPA2 | rs1965707 | SFTPA1 | rs1136450 | SFTPC | rs4715 | 0.003330483 | 0.00300 | 0.6 (0.4–0.8) | |
14 # | SFTPA1 | rs1059047 | SFTPA1 | rs1136450 | SFTPA1 | rs1136451 | 0.005263705 | 0.00500 | 0.7 (0.6–0.9) | |
15 # | SFTPA1 | rs1136451 | SFTPA1 | rs4253527 | SFTPC | rs4715 | 0.00126707 | 0.00100 | 0.5 (0.3–0.8) |
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Gandhi, C.K.; Chen, C.; Wu, R.; Yang, L.; Thorenoor, N.; Thomas, N.J.; DiAngelo, S.L.; Spear, D.; Keim, G.; Yehya, N.; et al. Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure. J. Clin. Med. 2020, 9, 1183. https://doi.org/10.3390/jcm9041183
Gandhi CK, Chen C, Wu R, Yang L, Thorenoor N, Thomas NJ, DiAngelo SL, Spear D, Keim G, Yehya N, et al. Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure. Journal of Clinical Medicine. 2020; 9(4):1183. https://doi.org/10.3390/jcm9041183
Chicago/Turabian StyleGandhi, Chintan K., Chixiang Chen, Rongling Wu, Lili Yang, Nithyananda Thorenoor, Neal J. Thomas, Susan L. DiAngelo, Debbie Spear, Garrett Keim, Nadir Yehya, and et al. 2020. "Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure" Journal of Clinical Medicine 9, no. 4: 1183. https://doi.org/10.3390/jcm9041183