Impact of genetic influence on serum total- and free 25-hydroxyvitamin-D in humans. Issue 183 (October 2018)

• Record Type: Journal Article
• Authors: Szili, Balázs; Szabó, Boglárka; Horváth, Péter; Bakos, Bence; Kirschner, Györgyi; Kósa, János P.; Toldy, Erzsébet; Putz, Zsuzsanna; Lakatos, Péter; Tabák, Ádám; Takács, István
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 183(2018)
• Page Start: 62
• Page End: 67
• Publication Date: 2018-10
• Subjects: Epidemiology/general population studies -- Genetic research/human association studies -- Diseases and disorders of/related to bone/other-vitamin D deficiency; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2018.05.007
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Serum 25-hydroxyvitamin D levels are determined primarily by environmental factors. The present study evaluates the genetic contribution to total- and free-25OHD levels. The selected SNPs account for 13.1% of the variance of t-25OHD levels. Two novel polymorphisms are responsible for the majority of the genetic effect. No SNPs exhibited association with f-25OHD levels. Abstract: Serum 25-hydroxyvitamin D /25OHD/ levels in humans are determined primarily by environmental factors such as UV-B radiation and diet, including vitamin D intake. Although some genetic determinants of 25OHD levels have been shown, the magnitude of this association has not yet been clarified. The present study evaluates the genetic contribution to total- /t-25OHD/ and free-25OHD /f-25OHD/ in a representative sample of the Hungarian population (n = 462). The study was performed at the end of winter to minimize the effect of sunlight, which is a major determinant of serum vitamin D levels. Single nucleotide polymorphisms (SNPs) of five genes playing major roles in vitamin D metabolism were investigated ( NADSYN1, DHCR7, GC, CYP2R1 and CYP24A1 ). The selected SNPs account for 13.1% of the variance of t-25OHD levels. More than half of the genetic effect on t-25OHD levels was explained by two polymorphisms (rs7935125 in NADSYN1 and rs2762941 in CYP24A1 ), which had not previously been investigated with respect to vitamin D metabolism. No SNPs exhibited association with f-25OHD levels. Unexpectedly, SNPs that showed univariate associations with vitamin D binding protein (DBP) l evels were not associated with f-25OHD levels questioning the biological significance of these polymorphisms. The present study shows that t-25OHD levels are significantly influenced by genetic factors, however, the clinical significance of this observation remains to be defined, as variation in f-25OHD levels are marginally explained by genetic effects.