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Associations between common variants in GC and DHCR7/NADSYN1 and vitamin D concentration in Chinese Hans

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Abstract

Recent studies have identified common variants in or near GC, CYP2R1 and NADSYN1/DHCR7 to be associated with 25-hydroxyvitamin D [25(OH)D] levels in European populations. We aimed to examine whether these variants also influence 25(OH)D levels in Chinese. Seven common variants were successfully genotyped and tested for associations with plasma 25(OH)D levels in a population-based cohort of 3,210 Chinese Hans from Beijing and Shanghai. Six common variants at GC (rs4588, rs7041, rs2282679 and rs1155563) and NADSYN1/DHCR7 (rs3829251 and rs1790349) loci were all significantly associated with lower plasma 25(OH)D levels (−0.036 ≤ β ≤ −0.076 per risk-allele, P ≤ 5.7 × 10−5), while CYP2R1-rs2060793 showed a trend toward association with 25(OH)D levels in the Shanghai subpopulation (P = 0.08), but not in the Beijing subpopulation (P = 0.82). Haplotype-based association analyses of the four GC variants showed that only the haplotype that contained all risk-alleles (TACC) was significantly associated with lower plasma 25(OH)D levels (β = −0.085, P = 2.3 × 10−9), while the haplotype containing the risk-alleles of rs4588 and rs2282679 (TATC) was marginally associated with lower 25(OH)D levels (β = −0.054, P = 0.0562) when compared with GCTA haplotype carrying the four protective alleles. Most notably, conditional analyses showed that only GC-rs4588 and GC-rs2282679 (r 2 = 0.97) remained significantly associated with 25(OH)D concentrations (P ≤ 1.9 × 10−5) after adjusting for the other two SNPs in GC. In conclusion, GC and NADSYN1/DHCR7 loci individually and collectively contribute to variation in plasma vitamin D levels in Chinese Hans.

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Acknowledgments

This work was supported by the research grants from the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [2009KIP401]; the Chief Scientist Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [SIBS2008006]; National Basic Research Program of China (973 Program) [2011CB504002]; the Knowledge Innovation Program Project of the Chinese Academy of Sciences [KSCX2-EW-R-10]; the National Natural Science Foundation of China [30930081 and 81021002]; National High Technology Research and Development Program (863 Program) [2009AA022704]; and supported by Xuhui Central Hospital, Shanghai, China [CRC2010008]. We are grateful to all the individuals who participated in the Nutrition and Health of Ageing Population in China project. We also thank our colleagues at the laboratory and the local centers for Disease Control staffs of Beijing and Shanghai.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-Yuan Rd., Shanghai, 200031, People’s Republic of China

    Ling Lu, Huaixing Li, Wei Gan, Chen Liu, Jingwen Zhu & Xu Lin

  2. Endocrine Branch, The Central Hospital of Xuhui District, Shanghai, 200031, People’s Republic of China

    Hongguang Sheng

  3. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Box 285, Hills Road, Cambridge, CB2 0QQ, UK

    Ruth J. F. Loos

  4. Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, People’s Republic of China

    Ling Lu, Hongguang Sheng, Huaixing Li, Wei Gan, Chen Liu, Jingwen Zhu & Xu Lin

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  1. Ling Lu
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  2. Hongguang Sheng
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  3. Huaixing Li
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  5. Chen Liu
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  7. Ruth J. F. Loos
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  8. Xu Lin
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Correspondence to Huaixing Li or Xu Lin.

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L. Lu and H. Sheng have contributed equally to this work.

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Lu, L., Sheng, H., Li, H. et al. Associations between common variants in GC and DHCR7/NADSYN1 and vitamin D concentration in Chinese Hans. Hum Genet 131, 505–512 (2012). https://doi.org/10.1007/s00439-011-1099-1

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  • DOI: https://doi.org/10.1007/s00439-011-1099-1

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