title: Interactions between serum vitamin D levels and vitamin D receptor gene FokI polymorphisms for renal function in patients with type 2 diabetes.
abstract: BACKGROUND
  We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.
  
  
  METHODS
  In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.
  
  
  RESULTS
  1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3 ~ 5 but not stage 1 ~ 2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65).
  
  
  CONCLUSIONS
  These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.
authors.affiliation: Division of Kidney, Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Akio
authors.initials: A
authors.lastname: Nakashima
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Urashima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mimura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kimura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kanazawa
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yokota
authors.forename: Masaya
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Sho
authors.initials: S
authors.lastname: Ishizawa
authors.forename: Rimei
authors.initials: R
authors.lastname: Nishimura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kurata
authors.forename: Yudo
authors.initials: Y
authors.lastname: Tanno
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tojo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kageyama
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ohkido
authors.forename: Kazunori
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D007677:Kidney Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D012621:Seasons; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood*; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific