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GC, CYP2R1 and DHCR7 genes associated with low vitamin D levels in China – 2012, 2013

Two articles from China on this page have the same conclusion


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

Swiss Med Wkly. 2012 July 16;142:w13636. doi: 10.4414/smw.2012.13636.
Zhang Y, Wang X, Liu Y, Qu H, Qu S, Wang W, Ren L.
Department of Pediatrics, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China. zhangyuling0000 at yahoo.com.cn

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.
PMID: 22801813

PDF is attached at the bottom of this page


An analysis of the association between the vitamin D pathway and serum 25-hydroxyvitamin D levels in a healthy Chinese population†

Journal of Bone and Mineral Research, Vol. 28 Issue 3 March 2013
Zeng Zhang 1,2,‡,
Jin-Wei He 2,‡,
Wen-Zhen Fu 2,
Chang-Qing Zhang 1,*,
Zhen-Lin Zhang 2,*
1 Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China
2 Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China
‡ The authors contribute equally to this work.
Email: Chang-Qing Zhang (zhangchangq@yahoo.com.cn), Zhen-Lin Zhang (zzl2002@medmail.com.cn)

Vitamin D deficiency has been recognized as a major public health issue worldwide. Recent studies have indicated that genetic factors might play an important role in determining serum 25-hydroxy vitamin D [25(OH)D] levels in Caucasians and African Americans. However, the genes that contribute to the variation in serum 25(OH)D levels in Chinese are unknown. In this study, we screened 15 key genes within the vitamin D metabolic pathway using 96 single-nucleotide polymorphism (SNP) markers in a group of 2,897 unrelated healthy Chinese subjects. Significant confounding factors that may influence the variability in serum 25(OH)D levels were used as covariates for association analyses. An association test for quantitative traits was performed to evaluate the association between candidate genes and serum 25(OH)D levels.

In the present study, variants and/or haplotypes in GC, CYP2R1 and DHCR7/NADSYN1 were identified as being associated with 25(OH)D levels. Participants with 3 or 4 risk alleles of the two variants (GC-rs4588 and CYP2R1-rs10766197) had an increased chance of presenting with a 25(OH)D concentration lower than 20 ng/mL (2.121, 1.586–2.836, p = 6.1 × 10−8) compared with those lacking the risk alleles.

Each additional copy of a risk allele was significantly associated with a 0.12-fold decrease in the log-25(OH)D concentration (p = 3.7 × 10−12). Haplotype TGA of GC rs705117-rs2282679-rs1491710, haplotype GAGTAC of GC rs842999-rs705120-rs222040-rs4588-rs7041-rs10488854, haplotype CA of GC rs1155563-rs222029, and haplotype AAGA of CYP2R1 rs7936142-rs12794714-rs2060793-rs16930609 were genetic risk factors toward a lower 25(OH)D concentration.

In contrary, haplotype TGGGCCC of DHCR7/NADSYN1 rs1790349-rs7122671-rs1790329-rs11606033-rs2276360-rs1629220-rs2282618 were genetic protective factors. The results suggest that the GC, CYP2R1 and DHCR7/NADSYN1 genes might contribute to variability in the serum 25(OH)D levels in a healthy Chinese population in Shanghai. These markers could be used as tools in Mendelian randomization analyses of vitamin D, and they could potentially be drug targets in the Chinese population in Shanghai. © 2013 American Society for Bone and Mineral Research.


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