The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Procedures
2.3. Blood Sampling and Genotyping
2.4. Statistical Analysis
3. Results
3.1. Demographic and Clinical Data
3.2. Association of COMT Polymorphisms with Negative Symptoms in Schizophrenia
3.3. Association of MAO-B Polymorphisms with Negative Symptoms in Schizophrenia
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Male Patients (n = 178) | Female Patients (n = 124) | Statistics | ||||
---|---|---|---|---|---|---|
Age | 41 (31;50) | 45 (38;53) | U = 9235.0; p = 0.016 | |||
BMI/kg | 27.5 (24.3;30.9) | 27.3 (23.6;32.4) | U = 11002.5; p = 0.964 | |||
First diagnosed/years | 23 (19;30) | 25 (19;33) | U = 10102.0; p = 0.210 | |||
Smoking | Non-smokers Smokers | 76 | 42.7% | 73 | 58.9% | χ2 = 7.649; df = 1; p = 0.006 |
102 | 57.3% | 51 | 41.1% | |||
Alcohol consumption | No | 148 | 83.1% | 114 | 91.9% | χ2 = 4.914; df = 1; p = 0.027 |
Yes | 30 | 16.9% | 10 | 8.1% | ||
History of drug abuse | No | 125 | 70.2% | 111 | 89.5% | χ2 = 15.927; df = 1; p < 0.001 |
Yes | 53 | 29.8% | 13 | 10.5% | ||
History of suicide attempts | No | 139 | 78.1% | 95 | 76.6% | χ2 = 0.091; df = 1; p = 0.762 |
Yes | 39 | 21.9% | 29 | 23.4% | ||
Antipsychotic therapy | Typical | 9 | 5.1% | 8 | 6.6% | χ2 = 2.230; df = 2; p = 0.328 |
Atypical | 123 | 69.5% | 74 | 61.2% | ||
Combined | 45 | 25.4% | 39 | 32.2% | ||
Antipsychotic dose/mg/day ꭞ | 550 (375;850) | 538 (350;900) | U = 10,818.5; p = 0.771 | |||
GAF scores | 50 (41;61) | 51 (41;65) | U = 11,016.0; p = 0.979 | |||
PANSS scores | 68 (60;79) | 67 (59;81) | U = 10,700.5; p = 0.653 | |||
CDSS scores | 1 (0;4) | 2 (0;6) | U = 9755.5; p = 0.080 | |||
CAINS scores | 23 (17;28) | 21 (15;26) | U = 9904.0; p = 0.129 | |||
BNSS scores | 29 (22;37) | 27 (21;35) | U = 9938.5; p = 0.141 | |||
RPAS scores | 19 (13;25) | 17 (12;22) | U = 9302.0; p = 0.020 | |||
RSAS scores | 12 (8;17) | 12 (7;17) | U = 10613.5; p = 0.571 | |||
Physical anhedonia | No | 141 | 79.2% | 78 | 62.9% | χ2 = 9.755; df = 1; p = 0.002 |
Yes | 37 | 20.8% | 46 | 37.1% | ||
Social anhedonia | No | 151 | 84.8% | 88 | 71.0% | χ2 = 8.509; df = 1; p = 0.004 |
Yes | 27 | 15.2% | 36 | 36.0% |
Clinical Scale Model (adj. R2) | CAINS R2 = 0.185 | BNSS R2 = 0.149 | RPAS R2 = 0.095 | RSAS R2 = 0.095 |
---|---|---|---|---|
Predictors | ||||
Age | F = 3.430; p = 0.065 | F = 0.956; p = 0.329 | F = 3.933; p = 0.048 | F = 4.476; p = 0.035 |
Sex | F = 0.717; p = 0.398 | F = 0.532; p = 0.467 | F = 6.391; p = 0.012 | F = 0.285; p = 0.594 |
Smoking | F = 1.483; p = 0.224 | F = 2.034; p = 0.155 | F = 2.752; p = 0.098 | F = 4.307; p = 0.039 |
Alcohol consumption | F = 0.863; p = 0.354 | F = 0.225; p = 0.635 | F = 0.047; p = 0.828 | F = 0.256; p = 0.613 |
History of drug abuse | F = 0.038; p = 0.845 | F = 0.581; p = 0.447 | F = 0.263; p = 0.609 | F = 0.315; p = 0.575 |
History of suicide attempts | F = 1.319; p = 0.252 | F = 1.213; p = 0.272 | F = 0.328; p = 0.567 | F = 0.263; p = 0.608 |
Antipsychotic dose ꭞ | F = 13.226; p < 0.001 | F = 11.314; p = 0.001 | F = 0.588; p = 0.444 | F = 1.671; p = 0.197 |
CAINS | BNSS | RPAS | RSAS | ||
---|---|---|---|---|---|
Male patients (n = 178) | |||||
COMT rs4680 | AA | 23 (18;29) | 28 (23;36) | 20 (13;27) | 13 (8;17) |
AG | 23 (16;28) | 29 (20;37) | 19 (14;25) | 11 (8;16) | |
GG | 23 (17;28) | 28 (23;35) | 16 (12;22) | 14 (8;18) | |
Statistics | H = 0.350; df = 2; p = 0.839 | H = 0.073; df = 2; p = 0.964 | H = 3.433; df = 2; p = 0.180 | H = 1.851; df = 2; p = 0.396 | |
COMT rs4680 | A | 23 (17;28) | 29 (23;36) | 20 (14;26) | 12 (8;16) |
G | 23 (17;28) | 29 (21;37) | 17 (17;23) | 12 (8;17) | |
Statistics | U = 15,428.5; p = 0.734 | U = 15,497.5; p = 0.788 | U = 14,072.5; p = 0.082 | U = 15,491.5; p = 0.783 | |
COMT rs4818 | CC | 23 (18;28) | 28 (23;36) | 20 (13;26) | 12 (8;17) |
CG | 22 (16;28) | 29 (20;37) | 19 (13;25) | 12 (7;16) | |
GG | 23 (19;28) | 29 (23;34) | 17 (13;20) | 14 (8;18) | |
Statistics | H = 0.559; df = 2; p = 0.756 | H = 0.110; df = 2; p = 0.946 | H = 1.896; df = 2; p = 0.387 | H = 1.168; df = 2; p = 0.558 | |
COMT rs4818 | C | 23 (17;28) | 29 (22;37) | 19 (13;25) | 12 (8;17) |
G | 23 (16;28) | 29 (22;37) | 18 (13;23) | 13 (8;17) | |
Statistics | U = 14,431.5; p = 0.744 | U = 14,495.5; p = 0.796 | U = 13,528.5; p = 0.196 | U = 14,669.5; p = 0.942 | |
COMT rs4818-rs4680 | CA | 23 (17;28) | 29 (23;36) | 20 (14;26) | 12 (8;16) |
GG | 23 (16;28) | 29 (22;37) | 18 (13;23) | 13 (8;18) | |
CG | 23 (17;28) | 28 (20;39) | 17 (12;24) | 12 (8;18) | |
Statistics | H = 0.164; df = 2; p = 0.921 | H = 0.089; df = 2; p = 0.956 | H = 3.027; df = 2; p = 0.220 | H = 0.255; df = 2; p = 0.880 | |
Female patients (n = 124) | |||||
COMT rs4680 | AA | 19 (15;23) | 14 (10;21) | 14 (10;21) | 11 (6;14) |
AG | 21 (15;26) | 18 (12;22) | 18 (12;22) | 12 (7;16) | |
GG | 24 (18;28) | 18 (11;23) | 18 (11;23) | 13 (7;17) | |
Statistics | H = 5.573; df = 2; p = 0.056 | H = 0.595; df = 2; p = 0.743 | H = 0.595; df = 2; p = 0.743 | H = 0.567; df = 2; p = 0.753 | |
COMT rs4680 | A | 20 (15;24) | 25 (19;33) | 17 (17;21) | 12 (7;15) |
G | 22 (16;28) | 27 (22;37) | 18 (12;22) | 13 (7;17) | |
Statistics | U = 6245.0; p = 0.015 | U = 6674.0; p = 0.094 | U = 7215.0; p = 0.475 | U = 7199; p = 0.458 | |
COMT rs4818 | CC | 19 (15;23) | 24 (18;32) | 17 (12;21) | 10 (6;14) |
CG | 22 (15;27) | 27 (20;38) | 18 (13;22) | 13 (8;17) | |
GG | 24 (18;29) | 27 (24;37) | 17 (10;23) | 13 (7;17) | |
Statistics | H = 6.838; df = 2; p = 0.033 | H = 2.650; df = 2; p = 0.266 | H = 0.223; df = 2; p = 0.895 | H = 2.789; df = 2; p = 0.248 | |
COMT rs4818 | C | 20 (15;24) | 27 (19;33) | 17 (12;21) | 11 (7;15) |
G | 23 (16;28) | 27 (22;37) | 18 (11;22) | 13 (7;17) | |
Statistics | U = 6063.0; p = 0.006 | U = 6649.0; p = 0.093 | U = 7388.0; p = 0.719 | U = 6732.0; p = 0.126 | |
COMT rs4818-rs4680 | CA | 20 (15;24) | 25 (19;33) | 17 (12;21) | 12 (7;15) |
GG | 23 (16;28) | 27 (22;37) | 18 (11;22) | 13 (7;17) | |
CG | 22 (15;25) | 29 (16;33) | 19 (13;22) | 11 (6;14) | |
Statistics | H = 7.579; df = 2; p = 0.023 | H = 3.108; df = 2; p = 0.211 | H = 0.648; df = 2; p = 0.723 | H = 3.065; df = 2; p = 0.216 |
CAINS | BNSS | RPAS | RSAS | ||
---|---|---|---|---|---|
Male patients (n = 178) | |||||
MAO-B rs1799836 | A | 24 (18;8) | 31 (23;37) | 19 (13;24) | 13 (8;17) |
G | 22 (17;28) | 27 (21;35) | 18 (12;23) | 12 (8;17) | |
Statistics | U = 2982.5; p = 0.137 | U = 2943.5; p = 0.107 | U = 3259.0; p = 0.553 | U = 3296.5; p = 0.637 | |
MAO-B rs6651806 | A | 24 (19;28) | 29 (24;37) | 18 (13;24) | 13 (8;17) |
C | 20 (13;28) | 24 (17;35) | 20 (13;23) | 11 (8;17) | |
Statistics | U = 2212.5; p = 0.036 | U = 2105.0; p = 0.013 | U = 2742.5; p = 0.846 | U = 2627.5; p = 0.544 | |
MAO-B rs1799836-rs6651806 | AA | 24 (19;29) | 32 (24;37) | 19 (13;26) | 13 (8;17) |
GC | 19 (13;25) | 24 (17;34) | 20 (13;25) | 11 (8;17) | |
GA | 23 (19;28) | 28 (25;35) | 17 (11;23) | 12 (8;17) | |
H = 5.720; df = 2; p = 0.057 | H = 7.229; df = 2; p = 0.027 | H = 1.558; df = 2; p = 0.459 | H = 0.576; df = 2; p = 0.750 | ||
Female patients (n = 124) | |||||
MAO-B rs1799836 | AA | 23 (14;26) | 28 (23;36) | 17 (10;23) | 14 (7;20) |
GA | 22 (16;28) | 27 (22;37) | 18 (13;22) | 13 (7;17) | |
GG | 20 (15;24) | 23 (19;31) | 17 (12;20) | 11 (6;14) | |
Statistics | H = 1.771; df = 2; p = 0.413 | H = 1.865; df = 2; p = 0.394 | H = 1.173; df = 2; p = 0.556 | H = 2.592; df = 2; p = 0.274 | |
MAO-B rs1799836 | A | 22 (15;26) | 28 (22;36) | 18 (11;22) | 13 (7;17) |
G | 21 (15;26) | 25 (20;33) | 17 (12;21) | 11 (7;16) | |
Statistics | U = 6662.5; p = 0.328 | U = 6620.5; p = 0.291 | U = 6880.5; p = 0.567 | U = 6381.5; p = 0.133 | |
MAO-B rs6651806 | AA | 21 (15;25) | 28 (21;33) | 18 (12;22) | 14 (7;19) |
AC | 21 (16;29) | 26 (20;40) | 17 (11;22) | 11 (6;14) | |
CC | 21 (14;27) | 25 (21;32) | 18 (13;19) | 9 (5;14) | |
Statistics | H = 0.533; df = 2; p = 0.766 | H = 0.401; df = 2; p = 0.818 | H = 0.848; df = 2; p = 0.654 | H = 4.331; df = 2; p = 0.115 | |
MAO-B rs6651806 | A | 21 (16;25) | 27 (21;34) | 18 (12;22) | 13 (7;17) |
C | 21 (15;27) | 26 (21;37) | 17 (12;20) | 11 (6;14) | |
Statistics | U = 6153.5; p = 0.946 | U = 6107.5; p = 0.872 | U = 5719.5; p = 0.347 | U = 5115.5; p = 0.031 | |
MAO-B rs1799836-rs6651806 | AA | 22 (15;26) | 28 (22;36) | 18 (11;22) | 13 (7;17) |
GC | 22 (15;27) | 26 (21;37) | 17 (11;20) | 11 (6;14) | |
GA | 20 (17;24) | 25 (19;32) | 18 (13;22) | 13 (9;17) | |
Statistics | H = 1.197; df = 2; p = 0.550 | H = 1.228; df = 2; p = 0.541 | H = 0.898; df = 2; p = 0.638 | H = 4.565; df = 2; p = 0.102 |
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Madzarac, Z.; Tudor, L.; Sagud, M.; Nedic Erjavec, G.; Mihaljevic Peles, A.; Pivac, N. The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia. Curr. Issues Mol. Biol. 2021, 43, 618-636. https://doi.org/10.3390/cimb43020045
Madzarac Z, Tudor L, Sagud M, Nedic Erjavec G, Mihaljevic Peles A, Pivac N. The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia. Current Issues in Molecular Biology. 2021; 43(2):618-636. https://doi.org/10.3390/cimb43020045
Chicago/Turabian StyleMadzarac, Zoran, Lucija Tudor, Marina Sagud, Gordana Nedic Erjavec, Alma Mihaljevic Peles, and Nela Pivac. 2021. "The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia" Current Issues in Molecular Biology 43, no. 2: 618-636. https://doi.org/10.3390/cimb43020045
APA StyleMadzarac, Z., Tudor, L., Sagud, M., Nedic Erjavec, G., Mihaljevic Peles, A., & Pivac, N. (2021). The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia. Current Issues in Molecular Biology, 43(2), 618-636. https://doi.org/10.3390/cimb43020045