Abstract
Vitamin D-binding protein (VDBP) is encoded by the GC gene and is an active participant in the control of bone metabolism. However, the effect of its major variants on VDBP concentration and bone mineral density (BMD) remains unclear. Our aim was to analyze the effect of major GC variants on serum VDBP concentration and BMD. We recruited individuals from the Health Workers Cohort Study, which includes employees of the Mexican Institute of Social Security (IMSS). A total of 1853 adults were included. The single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were genotyped to identify the three best characterized haplotypes of GC. Serum VBDP, 25(OH)D and BMD were also measured. Among women, the G allele of rs7041 was associated with higher VDBP and BMD compared to homozygous TT. The A allele of rs4588 was associated with lower VDBP and BMD compared to CC homozygous. In men, GC variants were only associated with VDBP levels. We did not observe an association between free/bioavailable 25(OH)D and BMD in men and women. Our results support an association of VDBP in bone health. The G and C alleles, from rs7041 and rs4588, respectively, are associated with high concentrations of VDBP and BMD in this sample of Mexican postmenopausal women.
Highlights
Vitamin D Binding Protein (VDBP) is the main transporter for Vitamin D (VitD) metabolites in serum; VDBP is known as GC globulin and it is encoded by the GC gene localized in the locus 4q11-q13 [1]
Our study shows data regarding the effect of the main haplotypes and respective alleles of the GC gene on serum VDBP concentrations and bone mineral density (BMD) in the Mexican population
When we looked at the haplotypes, serum VDBP concentration was significantly lower in heterozygous GC2/GC1S and GC2/GC1F compared to individual GC1S/GC1S
Summary
Vitamin D Binding Protein (VDBP) is the main transporter for Vitamin D (VitD) metabolites in serum; VDBP is known as GC globulin and it is encoded by the GC gene localized in the locus 4q11-q13 [1]. The GC gene is known for being highly polymorphic with more than 120 different allelic variants identified [2] Among these variants, three well-known haplotypes represent the most common and best characterized forms, which result from the combination of two single nucleotide polymorphisms (SNPs), rs7041 and rs4588. The rs4588 SNP is a C/A transversion resulting in the change of a threonine for lysine at position 436 The combination of these two SNPs results in the following haplotypes and amino acids composition, GC1F (rs7041T/rs4588-C; Asp/Lys); GC1S (rs7041-G/rs4588-C; Glu/Thr); and GC2 (rs7041-T/rs4588-A; Asp/Lys) [3]. The frequency of these three major haplotypes varies between populations. Previous reports have found the highest VDBP serum concentration in carriers of the GC1 haplotype (either 1F (rs7041-T/rs4588-C) or 1S (rs7041-G/rs4588-C)), and the lowest in homozygous for the GC2 (rs7041-T/rs4588-A) haplotype [5]
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