Vitamin-D Binding Protein Gene Polymorphisms and Serum 25-Hydroxyvitamin-D in a Turkish Population

Abstract

The rs7041 and rs4588 polymorphisms found in the GC gene, encoding vitamin D-binding protein (DBP), have distinct biochemical phenotypes. The aim of this study was to investigate vitamin D parameters with these polymorphisms, in individuals with possible vitamin D deficiency. The most common (49% of the cohort) genotype in rs7041 was GT, especially among individuals with high levels of free 25(OH)D calculated but with low levels of bioavailable 25(OH)D, and in rs4588 it was AC in particular among the individuals with low levels of bioavailable 25(OH)D. The most common phenotypes were Gc1s/2 (35.3%) and Gc1s/1s (31.4%), and Gc1f/1f was rare (5.9%). The variations in free and bioavailable 25(OH)D levels among healthy Turkish individuals may be attributed to the variations in total 25(OH)D as well as GC gene polymorphisms. The Turkish population shares a similarity for allele frequencies of rs7041 with the European population and similarity for allele frequencies of rs4588 with Gujarati Indians, and this may also be important in relation to certain ethnic populations showing associations between vitamin D and COVID-19.

Genetic influence on urinary vitamin D binding protein excretion and serum levels: a focus on rs4588 C>A polymorphism in the GC gene

“…The frequency of the rs4588-A allele, as reported in the NCBI 1000 Genomes Project Phase 3 sequence database, varies across populations, with rates of 0.24 in Europe, approximately 0.06 in African populations, and 0.20 globally (16). Our study's allele (14,15). GWAS studies have highlighted the significant effects of various GC polymorphisms in the vitamin D pathway (6,(17)(18)(19).…”

“…Given the lack of similar studies and available data, we conducted a sample size calculation to ensure an adequate number of participants with the rs4588-A allele. For this, we used the G*Power software, taking into account the allele frequencies reported in previous studies in Türkiye (14,15). This calculation factored in important parameters including a significance level (a) of 0.05, a statistical power (1-b) of 0.95, and the anticipated proportions of rs4588-C and rs4588-A allele carriers based on prior studies conducted in Turkey.…”

Single nucleotide polymorphisms in vitamin D binding protein and 25-hydroxylase genes affect vitamin D levels in adolescents of Arab ethnicity in Kuwait

“…VDBP has a higher affinity for 25(OH)D. Under normal conditions >99% of 25(OH)D is bound with proteins, mainly VDBP, and only 0.03% is in the unbound form (18). The binding affinity of the VDBP varies with the SNPs in the GC gene, with some variants having higher affinity for 25(OH)D than others (27,28). Different polymorphisms in the GC gene produce isotypes of VDBP with different affinities for 25(OH)D, and thus would affect its concentration in the blood (29).…”

Association of circulating serum free bioavailable and total vitamin D with cathelicidin levels among active TB patients and household contacts

“…In general, DBP gene variants control the amount of circulating DBP and alter binding affinity, free and bioavailable levels 34 , 35 . The DBP therefore plays a crucial role in the outcome of vitamin D status through its function as a reservoir of total vitamin D and as a regulator of free and bioavailable levels 36 . Accordingly, the Gc1F genotype, which is predominantly found in the African population, is believed to have a low concentration of the DBP gene and higher levels of free and bioavailable vitamin 37 .…”