Hypertensive Patients Exhibit Enhanced Thrombospondin-1 Levels at High-Altitude
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants and Clinical Evaluation
2.2. Thrombospondin-1 Circulating Levels Measurement
2.3. Receiver Operating Characteristic Curve
2.4. Correlation Analysis
2.5. Selection and Screening of the THBS1 and CD47 Gene Variants
2.5.1. SNP Genotyping in Highland and Sea-Level Populations
2.5.2. SNP–SNP Interactions and Allelic Influences of THBS1 and CD47 Gene Variants
2.6. Evaluation of THBS and CD Family Variants
2.6.1. Identifying Hypertension Associated Variants
2.6.2. Multi-Locus Interactions for Association Analysis
2.7. Protein–Protein Interactions Network
2.8. Statistical Analysis
3. Results
3.1. Evaluation of Demographic and Clinical Characteristics
3.2. Plasma THBS1 Levels Upregulate in Hypertensive Study Groups
3.3. Hypobaric Hypoxic Environment Enhances THBS1 Levels
3.4. THBS1 Levels Correlate with MAP
3.5. Genotype Distributions of THBS1 rs2228263 and Its Receptor CD47 rs9879947
3.5.1. Effect of Risk Allele on the Circulating Levels
3.5.2. Genetic Interactions between the THBS1 and CD47 SNPs Revealed the Causal Role of Risk Alleles
3.6. THBS-CD Family Genes Variants Regulate Hypertension under Hypobaric Hypoxia
3.6.1. Variants of THBS-CD Family Genes Associate with Hypertension at HA
3.6.2. Within Gene and Gene–Gene Interactions Define Etiology of Hypertension
3.6.3. Haplotypes Associate with Hypertension
3.7. Protein–Protein Interactions Inclined toward Hypertension
4. Discussion
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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Parameters | NHLs (n = 183) | HHLs (n = 166) | p-Value | NLLs (n = 486) | HLLs (n = 509) | p-Value |
---|---|---|---|---|---|---|
Sex | ||||||
Male | 48 (26%) | 55 (33%) | 363 (75%) | 326 (64%) | ||
Female | 135 (74%) | 111 (67%) | 123 (25%) | 183 (36%) | ||
Clinical Characteristics | ||||||
Age, years | 39.8 ± 9.0 | 40.9 ± 9.1 | NS | 38.0 ± 9.7 | 43.1 ± 7.7 | <0.0001 |
BMI, kg/m2 | 21.5 ± 2.8 | 21.7 ± 2.7 | NS | 23.1 ± 2.6 | 24.4 ± 2.4 | <0.0001 |
SBP, mm Hg | 111.3 ± 8.33 | 141.6 ± 16.0 | <0.0001 | 115.7 ± 6.0 | 157.1 ± 16.2 | <0.0001 |
DBP, mm Hg | 72.6 ± 7.5 | 88.9 ± 11.8 | <0.0001 | 76.2 ± 5.1 | 96.6 ± 8.5 | <0.0001 |
MAP, mm Hg | 85.5 ± 6.9 | 106.5 ± 12.4 | <0.0001 | 89.4 ± 5.1 | 116.8 ± 10.1 | <0.0001 |
High Altitude | |||||||
Gene (Variant Type) | SNP | Genotype/Allele | NHLs (n = 183) | HHLs (n = 166) | Logistic Regression Analysis | ||
n, (% Distribution) | χ2 | p-value | OR (95% CI) | ||||
THBS1 | rs2228263 | TT | 164 (89.6%) | 153 (92.1%) | - | - | Reference |
(Synonymous) | TC | 16 (8.7%) | 8 (4.8%) | 2.03 | 0.154 | 0.52 (0.21–1.27) | |
Co-dominant | CC | 3 (1.6%) | 5 (3.0%) | 0.88 | 0.346 | 2.04 (0.46–9.06) | |
TT + TC | 180 (98.4%) | 161 (97.0%) | - | - | Reference | ||
Recessive | CC | 3 (1.6%) | 5 (3.0%) | 1.08 | 0.298 | 2.19 (0.49–9.67) | |
T | 344 (94.0%) | 314 (94.6%) | - | - | Reference | ||
Allelic | C | 22 (6.0%) | 18 (5.4%) | 0.04 | 0.834 | 0.93 (0.48–1.78) | |
CD47 | rs9879947 | GG | 92 (50.2%) | 80 (48.2%) | - | - | Reference |
(3′UTR) | GA | 79 (43.1%) | 61 (36.7%) | 0.3 | 0.58 | 0.88 (0.56–1.38) | |
Co-dominant | AA | 12 (6.5%) | 25 (15.1%) | 5.81 | 0.016 | 2.56(1.19–5.51) | |
GG + GA | 171 (93.4%) | 141 (84.9%) | - | - | Reference | ||
Recessive | AA | 12 (6.6%) | 25 (15.1%) | 6.96 | 0.008 | 2.68 (1.28–5.57) | |
G | 263 (71.9%) | 221 (66.6%) | - | - | Reference | ||
Allelic | A | 103 (28.1%) | 111 (33.4%) | 2.46 | 0.116 | 1.29 (0.93–1.79) | |
Low Altitude | |||||||
Gene (Variant Type) | SNP | Genotype/Allele | NLLs (n = 486) | HLLs (n = 509) | Logistic Regression Analysis | ||
n, (% Distribution) | χ2 | p-value | OR (95% CI) | ||||
THBS1 | rs2228263 | TT | 412 (84.7%) | 431 (84.7%) | - | - | Reference |
(Synonymous) | TC | 53 (11%) | 69 (13.6%) | 1.22 | 0.268 | 1.23 (0.85–1.79) | |
Co-dominant | CC | 21 (4.3%) | 9 (1.7%) | 5.06 | 0.024 | 0.40 (0.18–0.89) | |
TT + TC | 465 (95.7%) | 500 (98.3%) | - | - | Reference | ||
Recessive | CC | 21 (4.3%) | 9 (1.7%) | 5.38 | 0.02 | 0.39 (0.18–0.80) | |
T | 877 (90.2%) | 931 (91.4%) | - | - | Reference | ||
Allelic | C | 95 (9.8%) | 87 (8.6%) | 0.96 | 0.326 | 0.86 (0.63–1.16) | |
CD47 | rs9879947 | GG | 167 (34.4%) | 187 (36.8%) | - | - | Reference |
(3′UTR) | GA | 244 (50.1%) | 232 (45.6%) | 1.36 | 0.244 | 0.85 (0.65–1.11) | |
Co-dominant | AA | 75 (15.5%) | 90 (17.6%) | 0.12 | 0.729 | 1.06 (0.74–1.53) | |
GG + GA | 411 (84.5%) | 419 (82.3%) | - | - | Reference | ||
Recessive | AA | 75 (15.5%) | 90 (17.7%) | 0.86 | 0.351 | 1.16 (0.84–1.62) | |
G | 578 (59.5%) | 606 (59.5%) | - | - | Reference | ||
Allelic | A | 394 (40.5%) | 412 (40.5%) | 0 | 0.963 | 0.99 (0.83–1.18) |
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Sharma, K.; Chanana, N.; Mohammad, G.; Thinlas, T.; Gupta, M.; Syed, M.A.; Das, R.S.; Pasha, Q.; Mishra, A. Hypertensive Patients Exhibit Enhanced Thrombospondin-1 Levels at High-Altitude. Life 2021, 11, 893. https://doi.org/10.3390/life11090893
Sharma K, Chanana N, Mohammad G, Thinlas T, Gupta M, Syed MA, Das RS, Pasha Q, Mishra A. Hypertensive Patients Exhibit Enhanced Thrombospondin-1 Levels at High-Altitude. Life. 2021; 11(9):893. https://doi.org/10.3390/life11090893
Chicago/Turabian StyleSharma, Kavita, Neha Chanana, Ghulam Mohammad, Tashi Thinlas, Mohit Gupta, Mansoor Ali Syed, Rajat Subhra Das, Qadar Pasha, and Aastha Mishra. 2021. "Hypertensive Patients Exhibit Enhanced Thrombospondin-1 Levels at High-Altitude" Life 11, no. 9: 893. https://doi.org/10.3390/life11090893