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

• 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
• Format: Article
• Published: W.B. Saunders Ltd 2020
• Subjects: RJ Pediatrics; Child health. Child health services
• Online Access: http://eprints.um.edu.my/36582/

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 (beta-8.11, P = 0.002) and Malaysian healthy children (beta-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.