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

Kong AN 1 , Fong CY 2 , Ng CC 3 , Mohamed AR 4 , Khoo TB 4 , Ng RL 5 Show all authors , Jalaludin MY 6 , Nadarajaw T 7

Affiliations 

  • 1 Division of Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
  • 2 Division of Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Electronic address: cyfong@ummc.edu.my
  • 3 Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
  • 4 Paediatric Neurology Unit, Women and Children's Hospital, Kuala Lumpur, Malaysia
  • 5 Division of Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia; Paediatric Department, Hospital Sultanah Bahiyah, Alor Setar, Kedah, Malaysia
  • 6 Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
  • 7 Paediatric Department, Hospital Sultanah Bahiyah, Alor Setar, Kedah, Malaysia
Seizure, 2020 Jul;79:103-111.
PMID: 32464532 DOI: 10.1016/j.seizure.2020.05.009

Abstract

PURPOSE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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