Kong Ann Nie, Fong Choong Yi, Ng Ching Ching, Mohamed Ahmad Rithauddin, Khoo Teik Beng, Ng Rui Lun, Jalaludin Muhammad Yazid, Nadarajaw Thiyagar
Division of Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
Division of Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
Seizure. 2020 Jul;79:103-111. doi: 10.1016/j.seizure.2020.05.009. Epub 2020 May 20.
Children with epilepsy (CWE) are at risk of vitamin D deficiency. Single nucleotide polymorphisms (SNPs) affecting the vitamin D pathway are potentially important risk factors for serum 25-hydroxyvitamin D [25(OH)D] concentration. The aims of our study were to evaluate the association of vitamin d-related SNPs to serum 25(OH)D concentrations in Malaysian CWE.
Cross-sectional study of Malaysian ambulant CWE on antiseizure medication for >1 year. Sixteen SNPs in 8 genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1, CYP27A1, CYP3A4, NADSYN1/DHCR7) were genotyped. Linear and logistic regression models and co-variates adjusted analyses were used. SNPs with significant associations were further analysed in a group of ethnically-matched healthy Malaysian children.
239 CWE were recruited (52.7% Malay, 24.3% Chinese and 23.0% Indian) with mean serum 25(OH)D of 58.8 nmol/L (SD 25.7). Prevalence of vitamin D deficiency (≤37.5 nmol/L) was 23.0%. Minor allele of GC-rs4588-A was associated with lower serum 25(OH)D in the meta-analysis of both CWE (β -8.11, P = 0.002) and Malaysian healthy children (β -5.08, P < 0.001), while VDR-rs7975232-A was significantly associated with reduced odds of vitamin D deficiency in Malay subgroup of CWE (OR: 0.16; 95% CI: 0.06-0.49; P = 0.001) and this association was not found in the healthy children group.
Our results suggest that GC-rs4588 is associated with lower serum 25(OH)D concentration in both Malaysian CWE and healthy children, while VDR-rs7975232A is associated with lower risk of vitamin D deficiency in Malaysian CWE of Malay ethnicity. Our findings may assist in the genetic risk stratification of low vitamin D status among CWE.
癫痫患儿（CWE）存在维生素D缺乏风险。影响维生素D代谢途径的单核苷酸多态性（SNP）可能是血清25-羟维生素D [25(OH)D]浓度的重要风险因素。我们研究的目的是评估马来西亚癫痫患儿中维生素D相关SNP与血清25(OH)D浓度的关联。
对服用抗癫痫药物超过1年的马来西亚门诊癫痫患儿进行横断面研究。对8个基因（GC、VDR、CYP2R1、CYP24A1、CYP27B1、CYP27A1、CYP3A4、NADSYN1/DHCR7）中的16个SNP进行基因分型。使用线性和逻辑回归模型以及协变量调整分析。在一组种族匹配的健康马来西亚儿童中对具有显著关联的SNP进行进一步分析。
招募了239例癫痫患儿（52.7%为马来人，24.3%为华人，23.0%为印度人），血清25(OH)D平均水平为58.8 nmol/L（标准差25.7）。维生素D缺乏（≤37.5 nmol/L）患病率为23.0%。在癫痫患儿（β -8.11，P = 0.002）和马来西亚健康儿童（β -5.08，P < 0.001）的荟萃分析中，GC基因rs4588-A的次要等位基因与较低的血清25(OH)D相关，而VDR基因rs7975232-A与癫痫患儿马来亚族亚组中维生素D缺乏几率降低显著相关（OR：0.16；95% CI：0.06 - 0.49；P = 0.00），且在健康儿童组中未发现这种关联。
我们的结果表明，GC基因rs4588与马来西亚癫痫患儿和健康儿童较低的血清25(OH)D浓度相关，而VDR基因rs7975232A与马来西亚马来族癫痫患儿较低的维生素D缺乏风险相关。我们的数据可能有助于对癫痫患儿中低维生素D状态进行遗传风险分层。
