Association of Voltage-Gated Potassium Channel Polymorphisms with the Risk and Prognosis of Epilepsy in the Saudi Population: A Case–Control Study
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Subjects and Design
2.2. Polymorphism Selection, DNA Extraction, and Genotyping
2.3. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Genetic Variants of KCN Genes
3.3. Genetic Association Between Genetic Variants of Voltage-Gated Potassium Channels and Epilepsy
3.4. Association of Clinical Factors of Epilepsy with Voltage-Gated K Channel Genes’ Variation
4. Discussion
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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General/Clinical Characteristics | Mean/Frequency | |
---|---|---|
Age at diagnosis | 9.7 ± 7.986 | |
BMI | 23.2 ± 7.789 | |
Duration of first seizure (sec) | 8.703 ± 14.032 | |
Gender | Male | 51% |
Female | 49% | |
Time to remission | No | 28.5% |
Yes (seizure-free immediately) | 52.3% | |
Yes (seizure-free within 6 months) | 18.7% | |
Epilepsy classification | Focal (partial) onset | 16% |
Generalized onset | 76% | |
Combined generalized and focal onset | 8% | |
Seizure classification | Motor | 94.6% |
Non-motor | 5.4% | |
History of febrile seizure | Yes | 11.9% |
No | 88.1% | |
Family history of epilepsy | Yes | 33.9% |
No | 66.1% | |
AED drug | Yes | 6% |
No | 94% | |
First drug responsiveness | Yes | 64% |
No | 36% | |
Relapse | Yes | 45% |
No | 55% | |
Periodic epilepsy | Yes | 21% |
No | 79% |
Gene | SNP ID | SNP Position a | Cases (n = 296) | Controls (n =293) | |||
---|---|---|---|---|---|---|---|
MA b | MAF c | HWE d p-Value | MAF c | HWE d p-Value | |||
KCNV2 | rs7029012 | 9:2717698 | C | 0.36 | 0.033 | 0.40 | 0.18 |
KCNAB1 | rs4295133 | 3:156516479 | A | 0.47 | 0.48 | 0.49 | 0.003 |
rs2720281 | 3:156512429 | G | 0.47 | 0.10 | 0.44 | 0.012 | |
rs17352408 | 3:156484880 | G | 0.28 | 0.19 | 0.29 | 0.032 | |
rs1546750 | 3:156468103 | C | 0.48 | 0.062 | 0.47 | 6 × 10−4 | |
rs2280561 | 3:156460417 | G | 0.44 | 1.00 | 0.47 | 1 × 10−3 | |
rs16826199 | 3:156452654 | G | 0.08 | 0.044 | 0.05 | 0.57 | |
KCNJ10 | rs12402969 | 1:160050447 | C | 0.01 | 1.00 | 0.01 | 0.017 |
rs1186675 | 1:160069294 | A | 0.02 | 0.11 | 0.03 | 0.019 |
Gene | SNP ID | Allelic and Genotypic Frequencies in Cases and Controls | |||
---|---|---|---|---|---|
Allele/Genotype | Cases (n = 495) | Controls (n = 497) | p-Value * | ||
KCNAB1 | rs3755631 | C | 539 (91%) | 550 (94% | 0.04 |
G | 53 (0.09%) | 34 (0.06%) | |||
rs4679773 | C | 300 (51%) | 330 (57%) | 0.04 | |
G | 288 (49%) | 250 (43%) | |||
KCNJ10 | rs2820585 | G/G | 204 (68.9%) | 225 (77.3%) | 0.034 |
A/G | 86 (29.1%) | 58 (19.9%) | |||
A/A | 6 (2%) | 8 (2.8%) | |||
rs946420 | C/C | 204 (69.2%) | 223 (77.2%) | 0.045 | |
C/A | 85 (28.8%) | 58 (20.1%) | |||
A/A | 6 (2%) | 8 (2.8%) | |||
rs1186679 | C/C | 203 (68.8%) | 226 (77.4%) | 0.021 | |
C/T | 87 (29.5%) | 58 (19.9%) | |||
T/T | 5 (1.7%) | 8 (2.7%) | |||
rs61822012 | A/A | 203 (69.3%) | 226 (77.7%) | 0.048 | |
A/G | 84 (28.7%) | 58 (19.9%) | |||
G/G | 6 (2%) | 7 (2.4%) | |||
rs1186685 | A | 495 (84%) | 513 (88%) | 0.04 | |
G | 97 (17%) | 71 (13%) | |||
rs12122979 | A/A | 205 (69.3%) | 229 (78.4%) | 0.018 | |
G/A | 85 (28.7%) | 55 (18.8%) | |||
G/G | 6 (2%) | 8 (2.7%) |
Gene | SNP ID | Age at Diagnosis | Duration of First Seizure | BMI | VIT.D | VIT B12 |
---|---|---|---|---|---|---|
KCNA2 | rs3887820 | 0.832 | 0.265 | 0.133 | 0.022 | 0.856 |
KCNV2 | rs10967705 | 0.510 | 0.005 | 0.784 | 0.794 | 0.742 |
rs1546750 | 0.045 | 0.776 | 0.249 | 0.904 | 0.320 | |
rs728382 | 0.866 | 0.069 | 0.244 | 0.326 | 0.031 | |
rs946420 | 0.01 | 0.189 | 0.146 | 0.093 | 0.469 | |
rs11265313 | 0.320 | 0.002 | 0.573 | 0.172 | 0.778 | |
rs61822012 | 0.01 | 0.330 | 0.118 | 0.093 | 0.469 | |
rs1186685 | 0.01 | 0.189 | 0.146 | 0.146 | 0.469 |
Gene | SNP ID | Gender | Relapse | History of Febrile Seizure | Periodic Seizure | Time to Remission | Drug Responsiveness | Drug Level | Family History of Epilepsy | Epilepsy Classification | Seizure Classification |
---|---|---|---|---|---|---|---|---|---|---|---|
KCNA1 | rs2227910 | 0.115 | 0.316 | 0.440 | 0.531 | 0.803 | 0.768 | 0.142 | 0.039 | 0.825 | 0.882 |
rs7974459 | 0.372 | 0.572 | 0.027 | 0.191 | 0.176 | 0.525 | 0.815 | 0.544 | 0.331 | 0.954 | |
KCNV2 | rs10967728 | 0.711 | 0.209 | 0.327 | 0.365 | 0.735 | 0.544 | 0.462 | 0.556 | 0.033 | 0.281 |
KCNA-B1 | rs992353 | 0.787 | 0.008 | 0.934 | 0.508 | 0.355 | 0.724 | 0.466 | 0.376 | 0.131 | 0.730 |
rs4679773 | 0.167 | 0.732 | 0.324 | 0.029 | 0.392 | 0.370 | 0.291 | 0.011 | 0.331 | 0.500 | |
rs1551066 | 0.665 | 0.750 | 0.599 | 0.175 | 0.513 | 0.207 | 0.678 | 0.093 | 0.020 | 0.997 | |
rs2280031 | 0.723 | 0.715 | 0.683 | 0.782 | 0.254 | 0.042 | 0.522 | 0.851 | 0.954 | 0.456 | |
KCNJ10 | rs1053074 | 0.004 | 0.486 | 0.409 | 0.086 | 0.134 | 0.791 | 0.128 | 0.545 | 0.647 | 0.606 |
rs2820585 | 0.203 | 0.787 | 0.321 | 0.039 | 0.643 | 0.008 | 0.279 | 0.448 | 0.652 | 0.381 | |
rs946420 | 0.176 | 0.741 | 0.205 | 0.153 | 0.781 | 0.006 | 0.209 | 0.403 | 0.896 | 0.297 | |
rs1186679 | 0.188 | 0.752 | 0.329 | 0.038 | 0.612 | 0.008 | 0.284 | 0.482 | 0.648 | 0.387 | |
rs4656873 | 0.440 | 0.798 | 0.313 | 0.010 | 0.049 | 0.879 | 0.082 | 0.947 | 0.482 | 0.786 | |
rs17375748 | 0.270 | 0.399 | 0.193 | 0.542 | 0.001 | 0.659 | 0.729 | 0.140 | 0.616 | 0.208 | |
rs61822012 | 0.217 | 0.651 | 0.197 | 0.161 | 0.669 | 0.004 | 0.203 | 0.425 | 0.888 | 0.290 | |
rs1890532 | 0.665 | 0.693 | 0.398 | 0.015 | 0.070 | 0.893 | 0.137 | 0.540 | 0.585 | 0.890 | |
rs1186689 | 0.324 | 0.984 | 0.020 | 0.536 | 0.417 | 0.084 | 0.072 | 1.000 | 0.712 | 0.436 | |
rs1186685 | 0.176 | 0.741 | 0.205 | 0.153 | 0.781 | 0.006 | 0.209 | 0.403 | 0.896 | 0.297 | |
rs12122979 | 0.251 | 0.225 | 0.437 | 0.512 | 0.591 | 0.056 | 0.372 | 0.047 | 0.902 | 0.629 | |
KCNJ9 | rs2753268 | 0.509 | 0.238 | 0.213 | 0.368 | 0.231 | 0.429 | 0.437 | 0.134 | 0.024 | 0.172 |
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Share and Cite
Alghamdi, M.A.; AL-Eitan, L.N.; Otaif, M.Y.; Rababa’h, D.M.; Alasmar, M.K.; Al-Garni, A.M.; Saleh, R.A.M.; Abdel Ghaffar, N.F. Association of Voltage-Gated Potassium Channel Polymorphisms with the Risk and Prognosis of Epilepsy in the Saudi Population: A Case–Control Study. Medicina 2025, 61, 396. https://doi.org/10.3390/medicina61030396
Alghamdi MA, AL-Eitan LN, Otaif MY, Rababa’h DM, Alasmar MK, Al-Garni AM, Saleh RAM, Abdel Ghaffar NF. Association of Voltage-Gated Potassium Channel Polymorphisms with the Risk and Prognosis of Epilepsy in the Saudi Population: A Case–Control Study. Medicina. 2025; 61(3):396. https://doi.org/10.3390/medicina61030396
Chicago/Turabian StyleAlghamdi, Mansour A., Laith N. AL-Eitan, Mansour Y. Otaif, Doaa M. Rababa’h, Maryam K. Alasmar, Abdulaziz M. Al-Garni, Rayyh A. M. Saleh, and Nawal F. Abdel Ghaffar. 2025. "Association of Voltage-Gated Potassium Channel Polymorphisms with the Risk and Prognosis of Epilepsy in the Saudi Population: A Case–Control Study" Medicina 61, no. 3: 396. https://doi.org/10.3390/medicina61030396
APA StyleAlghamdi, M. A., AL-Eitan, L. N., Otaif, M. Y., Rababa’h, D. M., Alasmar, M. K., Al-Garni, A. M., Saleh, R. A. M., & Abdel Ghaffar, N. F. (2025). Association of Voltage-Gated Potassium Channel Polymorphisms with the Risk and Prognosis of Epilepsy in the Saudi Population: A Case–Control Study. Medicina, 61(3), 396. https://doi.org/10.3390/medicina61030396