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The GC2 haplotype of the vitamin D binding protein is a risk factor for a low plasma 25-hydroxyvitamin D concentration in a Han Chinese population.

Background: The GC haplotype of the vitamin D binding protein (encoded by the GC gene) might be a risk factor to the vitamin D (VD) nutritional status for many populations, while evidences from the Chinese Han population are sparse. We test the association between vitamin D binding protein genotypes and VD status as well as the metabolic parameters of glucose and lipids in a Han Chinese population.

Methods: In a cross-sectional study conducted at a health examination centre (registered in ClinicalTrials.gov as QLS2013), 2641 adults were included and grouped according to their plasma 25-hydroxyvitamin D (25OHD) concentrations as VD deficient (VDD), insufficient (VDI), or sufficient (VDS). The rs7041 and rs4588 genotypes were analysed with a molecular beacon-based qPCR method using blood samples.

Results: Plasma 25OHD concentrations were lower in the GC 2/2, rs7041T/T, and rs4588A/A genotypes than the GC 1f/1s, rs7041G/T, and rs4588C/C genotypes ( P  <  0.05). After adjusting for confounders, the GC 2 haplotype increased the risk of low VD status ( P  <  0.05) in both genders. More genotypic models revealed the negative contributions of rs4588A than rs7041T to low VD status ( P  <  0.05). The combined rates of VDD and VDI were 80.2% in males and 86.1% in females. Compared with VDI, VDS, or both, VDD showed higher plasma concentrations of fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides in males ( P  <  0.05); however, no significant differences were found with regard to these parameters between the subgroups defined by the GC genotypes ( P  > 0.05).

Conclusions: In a Han Chinese population, the GC2 haplotype or more exactly rs4588A is a risk factor for low VD status but is not associated with glucose and lipid metabolic disorders, which are inversely correlated with the circulating 25OHD concentration in males.

Trial registration: The study was retrospectively registered in January 2018 as NCT03406234 in the ClinicalTrials.gov online system.

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