Publication: The genetic determinants of circulating C3-epimers of 25-hydroxyvitamin D
Issued Date
2018-06-01
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ISSN
22146237
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2-s2.0-85046397894
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Clinical and Translational Endocrinology. Vol.12, (2018), 36-41
Suggested Citation
Sirikunya Torugsa, Hataikarn Nimitphong, Daruneewan Warodomwichit, La or Chailurkit, Kriangsuk Srijaruskul, Suwannee Chanprasertyothin, Boonsong Ongphiphadhanakul The genetic determinants of circulating C3-epimers of 25-hydroxyvitamin D. Journal of Clinical and Translational Endocrinology. Vol.12, (2018), 36-41. doi:10.1016/j.jcte.2018.04.002 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45142
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Title
The genetic determinants of circulating C3-epimers of 25-hydroxyvitamin D
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Abstract
© 2018 The Authors Background: The complexity of vitamin D metabolites especially the contribution of C3-epimers of 25-hydroxyvitamin D (C3-epimers) in human sera remains unclear. We hypothesized that genetic polymorphisms in the vitamin D-related gene pathway contribute to variation in C3-epimer levels. Therefore, we investigated candidate single nucleotide polymorphisms (SNPs) concerning C3-epimer levels. Methods: The candidate SNPs, including DHCR7/NADSYN1 (rs12785878), CYP2R1 (rs2060793) and GC (rs2282679), were genotyped in 1727 members of the third project of the Electricity Generating Authority of Thailand 3/1 cohort investigation. Each SNP was tested under three genetic effects (dominant, recessive and additive models) concerning the levels of total serum 25(OH)D [the sum of 25(OH)D 2+3 and 3-epi-25(OH)D 2+3 ], non-C3-epimers [25(OH)D 2+3 ] and C3-epimers [3-epi-25(OH)D 2+3 ], using linear regression analysis. Results: Among the participants, the median (range) levels of non-C3-epimers and C3-epimers were 22.7 (6.4–49.2) ng/mL and 1.3 (0.01–14.2) ng/mL, respectively. In regression analysis, we found the genetic variation of two SNPs, the DHCR7/NADSYN1 (rs12785878; G > T) and GC (rs2282679; T > G) under additive genetic models, explained the variation of C3-epimer levels about 1.5% (p = 1.66 × 10 −7 ) and 1.1% (p = 1.10 × 10 −5 ), respectively. Interestingly, participants carrying the minor T-allele of rs12785878 exhibited a trend to increase C3-epimer levels, while those carrying the minor G-allele of rs2282679 exhibited a trend to decrease levels of both non-C3-epimers and C3-epimers. In addition, CYP2R1 (rs2060793; G > A) was clearly associated only with non-C3-epimer levels (p = 2.46 × 10 −8 ). In multivariate analyses, sex, age and BMI were predictors for variation in C3-epimer concentration; sex and age for variation in non-C3-epimers. Conclusion: To the best of our knowledge, this is the first study to demonstrate genetic models concerning the variation in C3-epimer levels. Our results emphasize that genetic determinants and the potential factors of C3-epimers differ from non-C3-epimers. This study contributes fundamental knowledge of the endogenous vitamin D pathway.