Interactions between serum vitamin D levels and vitamin D receptor gene FokI polymorphisms for renal function in patients with type 2 diabetes

PLoS One. 2012;7(12):e51171. doi: 10.1371/journal.pone.0051171. Epub 2012 Dec 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Deoxyribonucleases, Type II Site-Specific / genetics*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Genetic Predisposition to Disease
  • Glomerular Filtration Rate
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / physiopathology
  • Kidney Function Tests*
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*
  • Seasons
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood*
  • Young Adult

Substances

  • Receptors, Calcitriol
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D
  • endodeoxyribonuclease FokI
  • Deoxyribonucleases, Type II Site-Specific

Grants and funding

This research was supported by MEXT-Supported Program for the Strategic Research Foundation at Private Universities and by the Jikei University School of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.