Abstract
BackgroundThe 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.MethodsIn 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.ResultsPlasma 25OHD concentrations were lower in the GC2/2, rs7041T/T, and rs4588A/A genotypes than the GC1f/1s, rs7041G/T, and rs4588C/C genotypes (P < 0.05). After adjusting for confounders, the GC2 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).ConclusionsIn 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 registrationThe study was retrospectively registered in January 2018 as NCT03406234 in the ClinicalTrials.gov online system.
Highlights
The GC haplotype of the vitamin D binding protein might be a risk factor to the vitamin D (VD) nutritional status for many populations, while evidences from the Chinese Han population are sparse
The majority of 25-hydroxyvitamin D (25OHD) and other VD sterols are bound to the VD binding protein (VDBP, encoded by the GC gene) [15,16,17,18], which was initially named as group-specific protein [16]
Using an enzyme-linked immunosorbent assay (ELISA) kit with a polyclonal antibody, we did not find a the varied 25OHD concentrations might not result from the constant concentration of VDBP in healthy people [20, 43], the missense variations in rs7041 and rs4588 might affect the affinity of VDBP to VD sterols
Summary
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. The metabolic disorders associated with glucose and lipids might be affected by lower VD nutritional status [5,6,7,8,9,10,11]. Sunshine exposure (including season, latitude, exposure time of the day, and so on), skin colour, VD-rich food, and others affect the circulating concentration of 25OHD. It is intricately affected by its affinity to VDBP, which is determined by the isoforms of VDBP or the polymorphisms of GC. If GC1f and GC1s are combined, GC1/1 is equal to rs4588C/C, GC1/2 is equal to rs4588C/A, and GC2/2 is equal to rs4588A/A in genotypic frequencies
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