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

• Published in: Applied physiology, nutrition, and metabolism Vol. 41; no. 4; p. 345
• Main Authors: Almesri, Norah, Das, Nagalla S, Ali, Muhallab E, Gumaa, Khalid, Giha, Hayder Ahmed
• Format: Journal Article
• Language: English
• Published: Canada 01-04-2016
• Subjects: Adolescent; Adult; Alleles; Asian Continental Ancestry Group - 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; obésité; polymorphism; vitamin D receptor; Bahreïn; récepteur de vitamine D; Bahrain; protéine porteuse de vitamine D; obesity; polymorphisme; vitamin D binding protein
• ISSN: 1715-5320
• DOI: 10.1139/apnm-2015-0284

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.