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

Ji-Chang Zhou, Yumei Zhu, Chunmei Gong, Xiongshun Liang, Xiaoying Zhou, Yuanfei Xu, Deliang Lyu, Junluan Mo, Jian Xu, Jinping Song, Xiaoling Che, Shiqiang Sun, Changhua Huang, Xiao-Li Liu, Ji-Chang Zhou, Yumei Zhu, Chunmei Gong, Xiongshun Liang, Xiaoying Zhou, Yuanfei Xu, Deliang Lyu, Junluan Mo, Jian Xu, Jinping Song, Xiaoling Che, Shiqiang Sun, Changhua Huang, Xiao-Li Liu

Abstract

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 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).

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.

Keywords: Circulating 25-hydroxyvitamin D; Glucose; Han Chinese; Lipids; Single nucleotide polymorphism; Vitamin D binding protein.

Conflict of interest statement

This study was approved by the Ethic Committee of Shenzhen Centre of Chronic Disease Control, and all the subjects consented to participate the study.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Plasma 25OHD concentrations in males and females with genotypes of rs7041-rs4588 (a), rs7041 (b), and rs4588 (c) in vitamin D binding protein gene. Data are means ± SD, and differ without a common letter, P < 0.05. For the 6 genotypes of 1f/1f, 1s/1s, 1f/1s, 2/2, 1f/2, and 1s/2, n = 212, 98, 261, 88, 278, and 182 in males and 253, 116, 405, 140, 356, and 252 in females, respectively. For the G/G, G/T, and T/T genotypes of rs7041, n = 98, 443, and 578 in males and 116, 657, and 749 in females, respectively. For the A/A, A/C, and C/C genotypes of rs4588 (or GC2/2, GC1/2, and GC1/1 of VDBP), n = 88, 460, and 571 in males and 140, 608, and 774 in females, respectively
Fig. 2
Fig. 2
Logistic analysis on the contribution of vitamin D binding protein genotypes (1f/1f, 1 s/1 s, 2/2, 1f/2, or 1 s/2 against 1f/1 s) to the vitamin D (VD) statuses after adjusting for (gender,) age, body mass index, sampling month, smoking status, sunshine exposure time, sun protection use, and total vitamin D intakes. a, d, and g are VD insufficient (VDI) vs VD deficient (VDD), b, e, and h are VD sufficient (VDS) vs VDD, and c, f, and i are VDS vs VDI in both genders, male, and female, respectively. Data are odds ratio (OR, represented by ○, △, ●, and▲) ± 95% of confidential interval (CI). ○, P ≥ 0.1; △, 0.05 ≤ P < 0.1; ●, 0.01 ≤ P < 0.05; ▲, P < 0.01
Fig. 3
Fig. 3
Logistic analysis on the contribution of rs7041 in different genotypic models to the vitamin D (VD) statuses after adjusting for (gender,) age, body mass index, sampling month, smoking status, sunshine exposure time, sun protection use, and total vitamin D intakes. a, d, and g are VD insufficient (VDI) vs VD deficient (VDD), b, e, and h are VD sufficient (VDS) vs VDD, and c, f, and i are VDS vs VDI in both genders, male, and female, respectively. Data are odds ratio (OR, represented by ○, △, ●, and▲) ± 95% of confidential interval (CI). ○, P ≥ 0.1; △, 0.05 ≤ P < 0.1; ●, 0.01 ≤ P < 0.05; ▲, P < 0.01. Add., additive model; Alle., allelic model; Dom., dominant model; Hom., homozygous model; Rec., recessive model
Fig. 4
Fig. 4
Logistic analysis on the contribution of rs4588 in different genotypic models to the vitamin D (VD) statuses after adjusting for (gender,) age, body mass index, sampling month, smoking status, sunshine exposure time, sun protection use, and total vitamin D intakes. a, d, and g are VD insufficient (VDI) vs VD deficient (VDD), b, e, and h are VD sufficient (VDS) vs VDD, and c, f, and i are VDS vs VDI in both genders, male, and female, respectively. Data are odds ratio (OR, represented by ○, △, ●, and▲) ± 95% of confidential interval (CI). ○, P ≥ 0.1; △, 0.05 ≤ P < 0.1; ●, 0.01 ≤ P < 0.05; ▲, P < 0.01. Add., additive model; Alle., allelic model; Dom., dominant model; Hom., homozygous model; Rec., recessive model

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