The Ser290Asn and Thr715Pro Polymorphisms of the SELP Gene Are Associated with A Lower Risk of Developing Acute Coronary Syndrome and Low Soluble P-Selectin Levels in A Mexican Population †
Abstract
:1. Introduction
2. Subjects and Methods
2.1. Study Population
2.2. Laboratory Analyses
2.3. Genetic Analysis
2.4. Determination of P-Selectin Levels
2.5. Functional Prediction Analysis
2.6. Statistical Analysis
3. Results
3.1. Characteristics of the Study Population
3.2. Allele and Genotype Frequencies
3.3. Linkage Disequilibrium Analysis
3.4. Association of Polymorphisms with Plasma P-Selectin Levels
3.5. Functional Prediction
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
HDL-C | High-density lipoprotein–cholesterol |
LDL | Low-density lipoprotein–cholesterol |
SELP | P-selectin gene |
T2DM | Type 2 diabetes mellitus |
SNP | Single nucleotide polymorphism |
ACS | Acute coronary syndrome |
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ACS (n = 625) | Healthy Controls (n = 700) | p-Value | ||
---|---|---|---|---|
Median (percentile 25–75) | Median (percentile 25–75) | |||
Age (years) | 57.72 (51–65) | 54.39 (49–59) | <0.001 | |
BMI (kg/m2) | 27.3 (25–29) | 28.3 (26–31) | 0.001 | |
Blood pressure (mmHg) | Systolic | 130.61 (114–144) | 117.32 (106–126) | <0.001 |
Diastolic | 80.1 (70–90) | 72.47 (66–77) | <0.001 | |
Glucose (mg/dl) | 158.51 (102–188) | 98.73 (84–99) | <0.001 | |
Total cholesterol (mg/dl) | 164.22 (128–198) | 190.4 (164–210) | <0.001 | |
HDL-C (mg/dl) | 38.32 (32–44) | 44.6 (35–53) | <0.001 | |
LDL-C (mg/dl) | 106.4 (76–133) | 115.8 (94–134) | <0.001 | |
Triglycerides (mg/dl) | 169.2 (109–201) | 175.1 (112–208) | 0.218 | |
Gender n (%) | Male | 510 (82) | 463 (66) | <0.001 |
Female | 115 (18) | 237 (34) | ||
Smoking n (%) | Yes | 225 (35) | 155 (22) | <0.001 |
Hypertension | Yes | 355 (57) | 206 (29) | <0.001 |
Diabetes mellitus | Yes | 218 (35) | 68 (10) | <0.001 |
Dyslipidemia n (%) | Yes | 534 (85) | 501 (71) | <0.001 |
MAF | Model | OR (95%CI) | pC | ||||
---|---|---|---|---|---|---|---|
SELP G1057ASer290Asn (rs6131) | |||||||
GG | GA | AA | |||||
Control (n = 691) | 569 (0.823) | 115 (0.166) | 7 (0.010) | 0.09 | Co-dominant Dominant Recessive | 0.59 (0.38–0.92) 0.59 (0.39–0.90) 0.58 (0.12–2.83) | 0.047 0.014 0.49 |
ACS (n = 617) | 541 (0.877) | 73 (0.118) | 3 (0.005) | 0.06 | Over-dominant Additive | 0.61 (0.39–0.92) 0.62 (0.42–0.92) | 0.019 0.015 |
SELP G1980TLeu599Val (rs6133) | |||||||
GG | GT | TT | |||||
Control (n = 682) | 563 (0.825) | 114 (0.167) | 5 (0.007) | 0.09 | Co-dominant Dominant Recessive | 0.28 (0.02–3.32) 1.07 (0.73–1.58) 0.27 (0.02–3.26) | 0.46 0.73 0.26 |
ACS (n = 611) | 505 (0.827) | 105 (0.172) | 1 (0.002) | 0.09 | Over-dominant Additive | 1.12 (0.75–1.66) 1.02 (0.71–1.49) | 0.57 0.90 |
SELP A2331C Thr715Pro(rs6136) | |||||||
AA | AC | CC | |||||
Control (n = 685) | 580 (0.847) | 97 (0.141) | 8 (0.012) | 0.08 | Co-dominant Dominant Recessive | 0.63 (0.40–0.99) 0.61 (0.39–0.95) 0.36 (0.04–2.95) | 0.075 0.028 0.32 |
ACS (n = 607) | 537 (0.884) | 67 (0.110) | 3 (0.005) | 0.06 | Over-dominant Additive | 0.63 (0.40–0.99) 0.62 (0.41–0.94) | 0.044 0.023 |
Haplotypes | Thr715Pro | Leu599Val | Ser290Asn | ACS (n = 605) | Controls (n = 676) | OR | 95%CI | P |
---|---|---|---|---|---|---|---|---|
Hf | Hf | |||||||
H1 | Thr | Leu | Ser | 0.804 | 0.763 | 1.28 | 1.05–1.54 | 0.006 |
H2 | Thr | Val | Ser | 0.073 | 0.067 | 1.08 | 0.80–1.47 | 0.32 |
H3 | Pro | Leu | Ser | 0.057 | 0.077 | 0.72 | 0.52–0.99 | 0.022 |
H4 | Thr | Leu | Asn | 0.049 | 0.066 | 0.71 | 0.51–1.00 | 0.027 |
H5 | Pro | Val | Asn | 0.014 | 0.022 | 0.62 | 0.33–1.13 | 0.063 |
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Herrera-Maya, G.; Vargas-Alarcón, G.; Pérez-Méndez, O.; Posadas-Sánchez, R.; Masso, F.; Juárez-Cedillo, T.; Escobedo, G.; Vázquez-Montero, A.; Fragoso, J.M. The Ser290Asn and Thr715Pro Polymorphisms of the SELP Gene Are Associated with A Lower Risk of Developing Acute Coronary Syndrome and Low Soluble P-Selectin Levels in A Mexican Population . Biomolecules 2020, 10, 270. https://doi.org/10.3390/biom10020270
Herrera-Maya G, Vargas-Alarcón G, Pérez-Méndez O, Posadas-Sánchez R, Masso F, Juárez-Cedillo T, Escobedo G, Vázquez-Montero A, Fragoso JM. The Ser290Asn and Thr715Pro Polymorphisms of the SELP Gene Are Associated with A Lower Risk of Developing Acute Coronary Syndrome and Low Soluble P-Selectin Levels in A Mexican Population . Biomolecules. 2020; 10(2):270. https://doi.org/10.3390/biom10020270
Chicago/Turabian StyleHerrera-Maya, Gabriel, Gilberto Vargas-Alarcón, Oscar Pérez-Méndez, Rosalinda Posadas-Sánchez, Felipe Masso, Teresa Juárez-Cedillo, Galileo Escobedo, Andros Vázquez-Montero, and José Manuel Fragoso. 2020. "The Ser290Asn and Thr715Pro Polymorphisms of the SELP Gene Are Associated with A Lower Risk of Developing Acute Coronary Syndrome and Low Soluble P-Selectin Levels in A Mexican Population " Biomolecules 10, no. 2: 270. https://doi.org/10.3390/biom10020270