The Joint Link of the rs1051730 and rs1902341 Polymorphisms and Cigarette Smoking to Peripheral Artery Disease and Atherosclerotic Lesions of Different Arterial Beds
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Patients
2.2. Genetic Analysis
2.3. Statistical and Bioinformatics Analysis
3. Results
3.1. Associations of Polymorphisms rs1051730 and rs1902341 with Peripheral Artery Disease
3.2. Join Effects of the Studied Polymorphisms on the Risk of Peripheral Artery Disease
3.3. Relationship between the Polymorphisms and Plasma Lipids
3.4. The Impact of the Studied Polymorphisms on Other Atherosclerotic Lesions in PAD Patients
3.5. Functional Annotation of the Studied Polymorphisms
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Healthy Controls (N = 643) | PAD Patients (N = 620) | p-Value | |
---|---|---|---|---|
Age, mean ± standard deviation | 60.66 ± 7.93 | 62.18 ± 9.13 | 0.001 | |
Sex | Males, N (%) | 391 (60.81) | 532 (85.81) | <0.0001 |
Females, N (%) | 252 (39.19) | 88 (14.19) | ||
Body mass index (kg/m2). mean ± standard deviation | 27.07 ± 4.54 | 26.59 ± 6.36 | 0.12 | |
Smokers a, N (%) | 295 (47.2) | 324 (52.3) | 0.07 | |
Coronary artery disease, N (%) | - | 193 (30.63) | - | |
Hypertension, N (%) | - | 369 (58.57) | - | |
TC (mmol/L), Me (Q1; Q3) | NA | 5.07 (4.40; 5.60) | - | |
LDL-C (mmol/L), Me (Q1; Q3) | NA | 3.20 (2.10; 4.50) | - | |
HDL-C (mmol/L), Me (Q1; Q3) | NA | 1.18 (1.00; 1.57) | - | |
TG (mmol/L), Me (Q1; Q3) | NA | 1.50 (1.11; 2.20) | - |
SNP ID(Gene) | Geno-Type, Allele | Genotype/Allele Frequencies. N (%) | p(q) a | OR (95% CI) b | |
---|---|---|---|---|---|
Healthy Controls (N = 643) | PAD Patients (N = 620) | ||||
Entire groups | |||||
rs1902341 (OSBPL10) | C/C | 196 (30.5) | 204 (32.9) | 0.70 (0.70) | 1.00 |
C/T | 342 (53.2) | 302 (48.7) | 0.91 (0.63–1.32) | ||
T/T | 105 (16.3) | 114 (18.4) | 1.10 (0.68–1.77) | ||
T c | 0.429 | 0.427 | 0.93 (0.93) | 0.99 (0.85–1.16) | |
rs1051730 (CHRNA3) | G/G | 309 (48.1) | 228 (36.8) | 5.1 × 10−6 (3.1 × 10−5) | 1.00 |
G/A | 285 (44.3) | 302 (48.7) | 1.94 (1.36–2.75) | ||
A/A | 49 (7.6) | 90 (14.5) | 2.75 (1.59–4.77) | ||
A c | 0.325 | 0.389 | 0.0005 (0.0015) | 1.32 (1.13–1.55) | |
Smokers | |||||
rs1902341 (OSBPL10) | C/C | 96 (32.5) | 89 (27.5) | 0.05 (0.06) | 1.00 |
C/T | 157 (53.2) | 167 (51.5) | 1.38 (0.83–2.28) | ||
T/T | 42 (14.2) | 68 (21.0) | 2.28 (1.16–4.48) | ||
T c | 0.408 | 0.468 | 0.03 (0.043) | 1.27 (1.02–1.59) | |
rs1051730 (CHRNA3) | G/G | 141 (47.8) | 114 (35.2) | 0.008 (0.024) | 1.00 |
G/A | 134 (45.4) | 165 (50.9) | 1.67 (1.04–2.66) | ||
A/A | 20 (6.8) | 45 (13.9) | 2.97 (1.38–6.40) | ||
A c | 0.295 | 0.394 | 0.0003 (0.0015) | 1.55 (1.22–1.97) | |
Non-smokers | |||||
rs1902341 (OSBPL10) | C/C | 96 (29.1) | 115 (38.9) | 0.05 (0.06) | 1.00 |
C/T | 175 (53.0) | 135 (45.6) | 0.52 (0.28–0.95) | ||
T/T | 59 (17.9) | 46 (15.5) | 0.45 (0.18–1.10) | ||
T c | 0.444 | 0.383 | 0.03 (0.043) | 0.78 (0.62–0.98) | |
rs1051730 (CHRNA3) | G/G | 155 (47.0) | 114 (38.5) | 0.013 (0.026) | 1.00 |
G/A | 149 (45.1) | 137 (46.3) | 2.48 (1.30–4.72) | ||
A/A | 26 (7.9) | 45 (15.2) | 2.49 (0.87–7.07) | ||
A c | 0.305 | 0.383 | 0.003 (0.006) | 1.42 (1.12–1.80) |
№ | Genotype Combination (Diplotype) | PAD Patients | Healthy Controls | OR (95% CI) a | p b | q c | ||
---|---|---|---|---|---|---|---|---|
N | % | N | % | |||||
G1 | rs1051730G/G × rs1902341C/C | 74 | 11.9 | 104 | 16.2 | 0.70 (0.51–0.97) | 0.03 | 0.07 |
G2 | rs1051730G/G × rs1902341C/T | 112 | 18.1 | 158 | 24.6 | 0.68 (0.52–0.89) | 0.005 | 0.02 |
G3 | rs1051730G/G × rs1902341T/T | 42 | 6.8 | 47 | 7.3 | 0.92 (0.60–1.42) | 0.71 | 0.77 |
G4 | rs1051730G/A × rs1902341C/C | 98 | 15.8 | 78 | 12.1 | 1.36 (0.99–1.87) | 0.06 | 0.11 |
G5 | rs1051730G/A × rs1902341C/T | 149 | 24.0 | 159 | 24.7 | 0.96 (0.74–1.25) | 0.77 | 0.77 |
G6 | rs1051730G/A × rs1902341T/T | 55 | 8.9 | 48 | 7.5 | 1.21 (0.81–1.81) | 0.36 | 0.46 |
G7 | rs1051730A/A × rs1902341C/C | 32 | 5.2 | 14 | 2.2 | 2.45 (1.29–4.63) | 0.005 | 0.02 |
G8 | rs1051730A/A × rs1902341C/T | 41 | 6.6 | 25 | 3.9 | 1.75 (1.05–2.92) | 0.03 | 0.07 |
G9 | rs1051730A/A × rs1902341T/T | 17 | 2.7 | 10 | 1.6 | 1.78 (0.81–3.93) | 0.14 | 0.21 |
№ | Genotype Combination (Diplotypes) | PAD Patients | Healthy Controls | OR (95% CI) a | P b | Q c | ||
---|---|---|---|---|---|---|---|---|
N | % | N | % | |||||
Smokers | ||||||||
G1 | rs1051730GG × rs1902341CC | 28 | 8.6 | 47 | 15.9 | 0.50 (0.30–0.82) | 0.006 | 0.05 |
G2 | rs1051730GG × rs1902341CT | 60 | 18.5 | 73 | 24.7 | 0.69 (0.47–1.02) | 0.06 | 0.14 |
G3 | rs1051730GG × rs1902341TT | 26 | 8.0 | 21 | 7.1 | 1.14 (0.63–2.07) | 0.67 | 0.86 |
G4 | rs1051730GA × rs1902341CC | 47 | 14.5 | 42 | 14.2 | 1.02 (0.65–1.60) | 0.92 | 0.92 |
G5 | rs1051730GA × rs1902341CT | 82 | 25.3 | 73 | 24.7 | 1.03 (0.72–1.48) | 0.87 | 0.92 |
G6 | rs1051730GA × rs1902341TT | 36 | 11.1 | 19 | 6.4 | 1.82 (1.02–3.24) | 0.04 | 0.12 |
G7 | rs1051730AA × rs1902341CC | 14 | 4.3 | 7 | 2.4 | 1.80 (0.73–4.40) | 0.27 | 0.49 |
G8 | rs1051730AA × rs1902341CT | 25 | 7.7 | 11 | 3.7 | 2.16 (1.04–4.47) | 0.03 | 0.12 |
G9 | rs1051730AA × rs1902341TT | 6 | 1.9 | 2 | 0.7 | 2.40 (0.55–10.39) | 0.35 | 0.53 |
Non-smokers | ||||||||
G1 | rs1051730GG × rs1902341CC | 46 | 15.5 | 54 | 16.4 | 0.94 (0.61–1.44) | 0.78 | 0.78 |
G2 | rs1051730GG × rs1902341CT | 52 | 17.6 | 78 | 23.6 | 0.69 (0.46–1.02) | 0.06 | 0.18 |
G3 | rs1051730GG × rs1902341TT | 16 | 5.4 | 23 | 7.0 | 0.76 (0.39–1.47) | 0.42 | 0.54 |
G4 | rs1051730GA × rs1902341CC | 51 | 17.2 | 36 | 10.9 | 1.70 (1.07–2.69) | 0.02 | 0.09 |
G5 | rs1051730GA × rs1902341CT | 67 | 22.6 | 85 | 25.8 | 0.84 (0.58–1.22) | 0.36 | 0.54 |
G6 | rs1051730GA × rs1902341TT | 19 | 6.4 | 28 | 8.5 | 0.74 (0.40–1.35) | 0.33 | 0.54 |
G7 | rs1051730AA × rs1902341CC | 18 | 6.1 | 6 | 1.8 | 3.32 (1.34–8.93) | 0.01 | 0.09 |
G8 | rs1051730AA × rs1902341CT | 16 | 5.4 | 12 | 3.6 | 1.51 (0.70–3.26) | 0.29 | 0.54 |
G9 | rs1051730AA × rs1902341TT | 11 | 3.7 | 8 | 2.4 | 1.53 (0.62–3.76) | 0.48 | 0.54 |
Artery with Stenosis | rs1051730 | rs1902341 | ||
---|---|---|---|---|
Ultrasound | Angiography | Ultrasound | Angiography | |
Multifocal atherosclerosis (coronary and/or cerebral artery atherosclerosis) | 1.89 (1.10–3.25) A p = 0.019 | - | - | - |
Aorta (abdominal part) | 5.30 (1.85–15.19) A p = 7.0×10−4 | - | - | - |
Common iliac artery (right) | - | - | 3.14 (1.05–9.35) D p = 0.02 | - |
External iliac artery (left) | 7.19 (2.22–23.24) R p = 0.002 | - | - | - |
Proximal superficial femoral artery (right) | - | 8.52 (1.25–57.83) R p = 0.03 | 5.41 (1.60–18.31) D p = 0.001 | - |
Internal iliac artery (right) | - | 10.37 (1.39–77.61) D p = 0.02 | - | - |
Deep femoral artery (left) | - | - | - | 4.73 (1.66–13.52) R p = 0.04 |
Proximal superficial femoral artery (left) | - | 8.25 (2.16–31.46) Rp = 0.003 | - | - |
Distal superficial femoral artery (right) | - | 9.82 (1.42–67.81) R p = 0.01 | - | - |
Popliteal artery (left) | - | - | - | 2.07 (1.09–3.95) A p = 0.02 |
Posterior tibial artery (right) | - | 4.02 (1.06–15.28) OD p = 0.024 | - | - |
Posterior tibial artery (left) | - | - | - | 5.95 (1.21–29.37) R p = 0.03 |
Anterior tibial artery (right) | - | 5.81 (1.09–30.97) OD p = 0.018 | - | - |
Anterior tibial artery (left) | - | - | - | 7.90 (1.84–33.98) R p = 0.02 |
Dorsal foot artery (left) | - | - | 8.67 (1.03–72.86) A p = 0.01 |
SNP ID | Allele Assessed | Changes in Gene Expression | Whole Blood a | Whole Blood b | Tibial Artery b | |||
---|---|---|---|---|---|---|---|---|
q | Z | p | NES | p | NES | |||
rs1902341 | C | STT3B | 0.0015 * | −0.0183 * | - | - | - | - |
T | OSBPL10-AS1 | 0.0027 * | −3.0015 * | - | - | - | - | |
T | CMTM8 | 0.0089 * | −0.1641 * | - | - | - | - | |
- | SUGT1P2 | 0.0289 * | 0.2276 * | - | - | - | - | |
rs1051730 | A | CHRNA3 | - | - | - | - | 3.1 × 10−11 | −0.35 |
A | ADAMTS7 | - | - | - | - | 1.7 × 10−7 | 0.17 | |
A | PSMA4 | 1.2 × 10−90 | 20.2 | 1.5 × 10−9 | 0.09 | 0.0002 | 0.08 | |
A | IREB2 | 3.3 × 10−310 | −41.4 | 0.0001 | −0.07 | - | - | |
A | CTSH | 1.4 × 10−26 | 10.7 | - | - | - | - | |
A | AGPHD1 | 4.6 × 10−7 | −5.0 | - | - | - | - |
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Zhabin, S.; Lazarenko, V.; Azarova, I.; Klyosova, E.; Bykanova, M.; Chernousova, S.; Bashkatov, D.; Gneeva, E.; Polonikova, A.; Churnosov, M.; et al. The Joint Link of the rs1051730 and rs1902341 Polymorphisms and Cigarette Smoking to Peripheral Artery Disease and Atherosclerotic Lesions of Different Arterial Beds. Life 2023, 13, 496. https://doi.org/10.3390/life13020496
Zhabin S, Lazarenko V, Azarova I, Klyosova E, Bykanova M, Chernousova S, Bashkatov D, Gneeva E, Polonikova A, Churnosov M, et al. The Joint Link of the rs1051730 and rs1902341 Polymorphisms and Cigarette Smoking to Peripheral Artery Disease and Atherosclerotic Lesions of Different Arterial Beds. Life. 2023; 13(2):496. https://doi.org/10.3390/life13020496
Chicago/Turabian StyleZhabin, Sergey, Victor Lazarenko, Iuliia Azarova, Elena Klyosova, Marina Bykanova, Svetlana Chernousova, Daniil Bashkatov, Ekaterina Gneeva, Anna Polonikova, Mikhail Churnosov, and et al. 2023. "The Joint Link of the rs1051730 and rs1902341 Polymorphisms and Cigarette Smoking to Peripheral Artery Disease and Atherosclerotic Lesions of Different Arterial Beds" Life 13, no. 2: 496. https://doi.org/10.3390/life13020496