The GC, CYP2R1 and DHCR7 genes are associated with vitamin D levels in northeastern Han Chinese children

Abstract

Vitamin D deficiency is associated with risk in several diseases. Vitamin D status has high heritability, yet the genetic epidemiology of vitamin D or its metabolites has not been well studied. Our objective was to identify the relationship among three vitamin D-related genes (GC, CYP2R1 and DHCR7/NADSYN1) and the levels of 25(OH)D in northeastern Han Chinese children. A total of 506 northeastern Han Chinese children were enrolled in this study. Linear regression was used to examine the impact of 12 SNPs on 25(OH)D concentrations after adjustment for age, gender, BMI and regular usage of vitamin D, and Bonferroni's method was adopted for multiple corrections. The two SNPs in GC (rs222020, rs2298849), four SNPs in CYP2R1 (rs10741657, rs10766197, rs12794714 and rs1562902) and two SNPs in DHCR7/NADSYN1 (rs3829251, rs12785878) were significantly associated with plasma 25(OH)D concentrations under both additive and recessive models (P <0.05). The genotypes of the CYP2R1 rs2060793 polymorphism showed positive association with serum 25(OH)D status under all of the three genetic models even after correction for multiple comparison. This population-based study was the first to confirm the strong effects of the GC, CYP2R1 and DHCR7/NADSYN1 loci on circulating 25(OH)D concentrations in northeastern Han Chinese children.

Serum 25(OH)D and vitamin D status in relation to <i>VDR</i>, <i>GC</i> and <i>CYP2R1</i> variants in Chinese

“…Among several genetic variants of GC, rs7041 and rs4588, in exon 11, led to a Glu/Asp amino acid change at codon 416 and a Thy/Lys amino acid change at codon 420 [35], respectively. These two SNPs are the most commonly studied and repeatedly reported to be associated with lower levels of 25(OH)D. Our finding is in line with the results of several [11,17,19,23,31], but not all [12], recent studies that investigated the association between the genetic variants of GC and vitamin D. In a study of 3,210 Han Chinese from Beijing and Shanghai, Lu et al [11] found that the risk alleles of GC-rs2282679, rs4588 and rs7041 were significantly associated with lower levels of plasma 25(OH)D. The haplotype that contained all three risk alleles, and the C allele of rs1155563 was associated with lower levels of plasma 25(OH)D when compared with the haplotype that carried the four protective alleles. In 504 Chinese from Singapore, Robien et al [23] also found that GC-rs2282679, rs4588 and rs7041 were significantly associated with 25(OH)D concentration.…”

“…In addition, the Gc2-2 haplotype had the lowest concentrations of 25(OH)D among all the haplotypes consisting of GC-rs4588 and rs7041, which was consistent with our finding [23]. However, in a study of 506 Northeastern Han Chinese children recruited from outpatient clinic, Zhang et al [12] did not find a significant association of GC-rs2282679, rs4588, rs7041 with serum levels of 25(OH)D after Bonferroni correction for multiple testing. The possible explanations for these discrepancies include: (1) the participants of their study were recruited from the outpatient clinic, which might have confounded the interpretation of the results; (2) more than half of the participants were on regular vitamin D supplementation, although participants received vitamin D treatment or supplementation above 400 IU/d were excluded.…”

“…The CYP2R1-rs12794714 is less investigated compared with other SNPs in previous studies. Two previous studies found that the risk allele of CYP2R1-rs12794714 was associated with lower levels of 25(OH)D [12,23]. The reason for non-significant association between CYP2R1-rs12794714 and serum levels of 25(OH)D in the present study is unknown.…”

“…Thus, genetic variants in the vitamin D metabolism pathway are widely investigated. Recently, genetic association studies including genome-wide association studies (GWAS) have identified that a majority of SNPs are associated with circulating levels of 25(OH) D and vitamin D deficiency [11,12,[16][17][18][19][20][21][22][23]. However, these genetic association studies are mainly conducted in Western populations, and it remains to be confirmed whether these genetic variants have similar effects in Chinese.…”

Nutrition assessment of vitamin A and vitamin D in northeast Chinese population based-on SPE/UPLC/PDA

“…In China, the prevalence of serum 25OHD 3 deficiency is higher than 50% in all age groups [25,26], reaching 85.8%, 97%, and 89.7% in schoolaged students, adolescents, and adults, respectively, in some remote and low-income regions [27][28][29]. The prevalence of vitamin D deficiency in schoolchildren (ages 7 to 11 y) is 56.4% in 2013 [30] and 45.85% of (ages 1 to 10 y) [31] in Harbin. The prevalence of suboptimal vitamin D (vitamin D deficiency and insufficiency) is 74.7% (ages 20 to 74 y) [32] and 87.35% (ages 1 to 10 y) [31] in Harbin.…”