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Association of common genetic variants with vitamin D status in Malaysian children with epilepsy

•GC-rs4588 polymorphism is associated with lower 25(OH)D concentrations in both Malaysian children with epilepsy and Malaysian healthy children.•VDR-rs7975232-A (ApaI) polymorphism is associated with lower risk of vitamin D deficiency in Malaysian children with epilepsy of Malay ethnicity.•Genetic f...

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Published in:Seizure (London, England) England), 2020-07, Vol.79, p.103-111
Main Authors: Kong, Ann Nie, Fong, Choong Yi, Ng, Ching Ching, Mohamed, Ahmad Rithauddin, Khoo, Teik Beng, Ng, Rui Lun, Jalaludin, Muhammad Yazid, Nadarajaw, Thiyagar
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Language:English
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Summary:•GC-rs4588 polymorphism is associated with lower 25(OH)D concentrations in both Malaysian children with epilepsy and Malaysian healthy children.•VDR-rs7975232-A (ApaI) polymorphism is associated with lower risk of vitamin D deficiency in Malaysian children with epilepsy of Malay ethnicity.•Genetic factors play a role in the vitamin D status among children with epilepsy. 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.
ISSN:1059-1311
1532-2688
DOI:10.1016/j.seizure.2020.05.009