title: Common genetic variation in vitamin D metabolism is associated with liver stiffness.
abstract: Recently, genome-wide studies identified genetic variants that affect serum 25-hydroxyvitamin D levels in healthy populations (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, at CYP2R1; and rs7041, at vitamin D binding protein, GC). Because vitamin D deficiency is associated with advanced liver disease, we hypothesized that these variants are associated with 25(OH)-vitamin D levels and liver fibrosis. Overall, 712 Caucasian patients with chronic liver diseases were included. Liver fibrosis was assessed by transient elastography (TE) and/or histology. Serum levels of 25(OH)-vitamin D were correlated with TE and fibrosis stages. Genotypes were determined using TaqMan assays and tested for association with vitamin D and liver stiffness. Serum 25(OH)-vitamin D levels were inversely correlated with liver stiffness and histology (P < 0.001). Homozygous carriers of the rare DHCR7 allele or the common CYP2R1 allele presented with reduced 25(OH)-vitamin D levels (P < 0.05). The variant rs12785878 in the DHCR7 locus was associated with liver stiffness in both patients with TE <7.0 kPa and TE between 7.0 and 9.5 kPa. 25(OH)-vitamin D levels correlated with sunshine hours at the time of inclusion (P < 0.001).
  
  
  CONCLUSIONS
  Common variation in 25(OH)-vitamin D metabolism is associated with liver stiffness in patients presenting with low to moderately increased elasticity. Although the susceptible DHCR7 genotype confers small risk, we speculate that the observed stiffness differences indicate a stronger influence of 25(OH)-vitamin D on initiation rather than progression of hepatic fibrosis.
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg, Germany. frank.gruenhage@uks.eu
authors.forename: Frank
authors.initials: F
authors.lastname: Grünhage
authors.forename: Katrin
authors.initials: K
authors.lastname: Hochrath
authors.forename: Marcin
authors.initials: M
authors.lastname: Krawczyk
authors.forename: Aksana
authors.initials: A
authors.lastname: Höblinger
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisel
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D004548:Elasticity; D054459:Elasticity Imaging Techniques; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016014:Linear Models; D008103:Liver Cirrhosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018709:Statistics, Nonparametric; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics; D014809:Vitamin D-Binding Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase