title: Levels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity Study.
abstract: BACKGROUND
  Low levels of 25(OH) vitamin D are associated with various age-related diseases and mortality, but causality has not been determined. We investigated vitamin D levels in the offspring of nonagenarians who had at least one nonagenarian sibling; these offspring have a lower prevalence of age-related diseases and a higher propensity to reach old age compared with their partners.
  
  
  METHODS
  We assessed anthropometric characteristics, 25(OH) vitamin D levels, parathyroid hormone levels, dietary vitamin D intake and single nucleotide polymorphisms (SNPs) associated with vitamin D levels. We included offspring (n = 1038) of nonagenarians who had at least one nonagenarian sibling, and the offsprings' partners (n = 461; controls) from the Leiden Longevity Study. We included age, sex, body mass index, month during which blood sampling was performed, dietary and supplemental vitamin D intake, and creatinine levels as possible confounding factors.
  
  
  RESULTS
  The offspring had significantly lower levels of vitamin D (64.3 nmol/L) compared with controls (68.4 nmol/L; p = 0.002), independent of possible confounding factors. There was no difference in the levels of parathyroid hormone between groups. Compared with controls, the offspring had a lower frequency of a genetic variant in the CYP2R1 gene (rs2060793) (p = 0.04). The difference in vitamin D levels between offspring and controls persisted over the 2 most prevalent genotypes of this SNP.
  
  
  CONCLUSIONS
  Compared with controls, the offspring of nonagenarians who had at least one nonagenarian sibling had a reduced frequency of a common variant in the CYP2R1 gene, which predisposes people to high vitamin D levels; they also had lower levels of vitamin D that persisted over the 2 most prevalent genotypes. These results cast doubt on the causal nature of previously reported associations between low levels of vitamin D and age-related diseases and mortality.
authors.forename: Raymond
authors.initials: R
authors.lastname: Noordam
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Pardis
authors.initials: P
authors.lastname: Pedram
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Maier
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.forename: Johannes
authors.initials: J
authors.lastname: van Pelt
authors.forename: Edith J
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Martinette T
authors.initials: MT
authors.lastname: Streppel
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Marian
authors.initials: M
authors.lastname: Beekman
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
mesh_terms: D032721:Adult Children; D000369:Aged, 80 and over; D016022:Case-Control Studies; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D004032:Diet; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008136:Longevity; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D010281:Parathyroid Hormone; D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase