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The prevalence of vitamin D deficiency, presenting as hypocalcemic seizures or rickets in children, is increasing worldwide due to insufficient vitamin D intake and lack of exposure to sunshine.  However, considering that relatively few children with low 25-hydroxyvitamin D [25(OH)D] levels manifest symptoms, it is possible that genetic factors may predispose individuals to vitamin D deficiency.  Recent twin studies have reported that the level of serum of 25(OH)D is influenced by genetic factors.  In addition, genome-wide association studies and candidate gene studies have revealed that several vitamin D-related genes, including VDR, GC, NADSYN1, CYP2R1, CYP24A1, CYP27B1, and C10orf88 contribute to variations in serum 25(OH)D levels.  To investigate whether genetic predisposition contributes to vitamin D deficiency, we analyzed polymorphisms in vitamin D-related genes in 30 Japanese patients with vitamin D deficiency presenting at less than 4 years of age, along with 66 controls.  A χ(2) test showed that the genotype frequencies of BsmI polymorphism in VDR and rs10898191 in NADSYN1 were significantly different between the two groups. The allele frequencies of BsmI, ApaI, TaqI in VDR, rs10898191 in NADSYN1, and rs705117 in GC were also significantly different.  In particular, the frequency of the BAtS haplotype in VDR was significantly increased in the patient group relative to controls (p = 0.0014; odds ratio, 5.61; 95% confidence interval 1.92 - 16.40).  Although this is a small study, our findings suggest that VDR, NADSYN1, and GC polymorphisms may be linked to the manifestation of vitamin D deficiency in Japanese children.

Association of vitamin D-related gene polymorphisms with manifestation of vitamin D deficiency in children