Independent associations of polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes with obesity and plasma 25OHD3 levels demonstrate sex dimorphism

Appl Physiol Nutr Metab. 2016 Apr;41(4):345-53. doi: 10.1139/apnm-2015-0284. Epub 2015 Nov 30.

Abstract

We investigated a possible association between polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes and obesity in Bahraini adults. For this purpose, 406 subjects with varying body mass indexes (BMIs) were selected. Plasma levels of 25-hydroxyvitamin D3 (25OHD3) were measured by chemiluminescence immunoassay. Six single nucleotide polymorphisms, 2 in the VDR gene (rs731236 TC and rs12721377 AG) and 4 in the GC gene (rs2282679 AC, rs4588 CA, rs7041 GT, and rs2298849 TC), were genotyped by real-time polymerase chain reaction. We found that the rs7041 minor allele (G) and rare genotype (GG) were associated with higher BMI (p = 0.007 and p = 0.012, respectively), but they did not influence 25OHD3 levels. However, the minor alleles of rs2282679 (A) and rs4588 (C) were associated with low 25OHD3 plasma levels (p = 0.039 and p = 0.021, respectively), but not with BMI. Having categorized the subjects based on their sex, we found that (i) rs7041 GG associated with high BMI in females (p = 0.003), (ii) rs4588 CC associated with high BMI in females (p = 0.034) and low 25OHD3 levels in males (p = 0.009), and (iii) rs12721377 AA associated with low 25OHD3 levels in females (p = 0.039). Notably, none of the common haplotypes (6 in the GC gene and 3 in the VDR gene) were associated with BMI. Therefore, polymorphisms in the GC (rs2282679, rs4588, rs7041) and VDR (rs12721377) genes were independently associated with obesity and 25OHD3 levels with a clear sex dimorphism.

Keywords: Bahrain; Bahreïn; obesity; obésité; polymorphism; polymorphisme; protéine porteuse de vitamine D; récepteur de vitamine D; vitamin D binding protein; vitamin D receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Asian People / genetics
  • Bahrain
  • Body Mass Index
  • Cross-Sectional Studies
  • Female
  • Genotyping Techniques
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Receptors, Calcitriol / genetics*
  • Receptors, Calcitriol / metabolism
  • Sex Factors*
  • Vitamin D / blood*
  • Vitamin D-Binding Protein / genetics*
  • Vitamin D-Binding Protein / metabolism
  • Young Adult

Substances

  • Receptors, Calcitriol
  • VDR protein, human
  • Vitamin D-Binding Protein
  • Vitamin D