Abstract
Objective:
Observational studies have examined the link between vitamin D deficiency and obesity traits. Some studies have reported associations between vitamin D pathway genes such as VDR, GC and CYP27B1 with body mass index (BMI) and waist circumference (WC); however, the findings have been inconsistent. Therefore, we investigated the involvement of vitamin D metabolic pathway genes in obesity-related traits in a large population-based study.
Methods:
We undertook a comprehensive analysis between 100 tagging single nucleotide polymorphisms (tagSNPs) in genes encoding for DHCR7, CYP2R1, VDBP, CYP27B1, CYP27A1, CYP24A1, VDR and RXRG, and obesity traits in 5224 participants (aged 45 years) in the 1958 British birth cohort (1958BC). We further extended our analyses to investigate the associations between SNPs and obesity traits using the summary statistics from the GIANT (Genetic Investigation of Anthropometric Traits) consortium (n=123 865).
Results:
In the 1958BC (n=5224), after Bonferroni correction, none of the tagSNPs were associated with obesity traits except for one tagSNP from CYP24A1 that was associated with waist–hip ratio (WHR) (rs2296239, P=0.001). However, the CYP24A1 SNP was not associated with BMI-adjusted WHR (WHRadj) in the 1958BC (rs2296239, P=1.00) and GIANT results (n=123 865, P=0.18). There was also no evidence for an interaction between the tagSNPs and obesity on BMI, WC, WHR and WHRadj in the 1958BC. In the GIANT consortium, none of the tagSNPs were associated with obesity traits.
Conclusions:
Despite a very large study, our findings suggest that the vitamin D pathway genes are unlikely to have a major role in obesity-related traits in the general population.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Flegal KM, Carroll MD, Ogden CL, Curtin LR . Prevalence and trends in obesity among US adults, 1999–2008. JAMA 2010; 303: 235–241.
Berghofer A, Pischon T, Reinhold T, Apovian CM, Sharma AM, Willich SN . Obesity prevalence from a European perspective: a systematic review. BMC Public Health 2008; 8: 200.
Earthman CP, Beckman LM, Masodkar K, Sibley SD . The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications. Int J Obes (Lond) 2012; 36: 387–396.
Foss YJ . Vitamin D deficiency is the cause of common obesity. Med Hypotheses 2009; 72: 314–321.
Holick MF, Chen TC . Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008; 87: 1080S–1086SS.
Berry D, Hyppönen E . Determinants of vitamin D status: focus on genetic variations. Curr Opin Nephrol Hypertens 2011; 20: 331–336.
Jiang H, Xiong DH, Guo YF, Shen H, Xiao P, Yang F et al. Association analysis of vitamin D-binding protein gene polymorphisms with variations of obesity-related traits in Caucasian nuclear families. Int J Obes (Lond) 2007; 31: 1319–1324.
Hirai M, Suzuki S, Hinokio Y, Hirai A, Chiba M, Akai H et al. Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance. J Clin Endocrinol Metab 2000; 85: 1951–1953.
Malecki MT, Klupa T, Wolkow P, Bochenski J, Wanic K, Sieradzki J . Association study of the vitamin D: 1alpha-hydroxylase (CYP1alpha) gene and type 2 diabetes mellitus in a Polish population. Diabetes Metab 2003; 29: 119–124.
Ochs-Balcom HM, Chennamaneni R, Millen AE, Shields PG, Marian C, Trevisan M et al. Vitamin D receptor gene polymorphisms are associated with adiposity phenotypes. Am J Clin Nutr 2011; 93: 5–10.
Dorjgochoo T, Shi J, Gao YT, Long J, Delahanty R, Xiang YB et al. Genetic variants in vitamin D metabolism-related genes and body mass index: analysis of genome-wide scan data of approximately 7000 Chinese women. Int J Obes (Lond) 2012; 36: 1252–1255.
Bosse Y, Lemire M, Poon AH, Daley D, He JQ, Sandford A et al. Asthma and genes encoding components of the vitamin D pathway. Respir Res 2009; 10: 98.
Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU et al. Association analyses of 249 796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42: 937–948.
Lindgren CM, Heid IM, Randall JC, Lamina C, Steinthorsdottir V, Qi L et al. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genet 2009; 5: e1000508.
Power C, Atherton K, Strachan DP, Shepherd P, Fuller E, Davis A et al. Life-course influences on health in British adults: effects of socio-economic position in childhood and adulthood. Int J Epidemiol 2007; 36: 532–539.
Power C, Elliott J . Cohort profile: 1958 British birth cohort (National Child Development Study). Int J Epidemiol 2006; 35: 34–41.
Atherton K, Fuller E, Shepherd P, Strachan DP, Power C . Loss and representativeness in a biomedical survey at age 45 years: 1958 British birth cohort. J Epidemiol Community Health 2008; 62: 216–223.
Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263–265.
The Wellcome Trust Case Control Consortium. Genome-wide association study of 14 000 cases of seven common diseases and 3000 shared controls. Nature 2007; 447: 661–678.
Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 2009; 41: 703–707.
World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894: 1–253.
Smith GD, Ebrahim S . Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol 2004; 33: 30–42.
Berry DJ, Vimaleswaran KS, Whittaker JC, Hingorani AD, Hyppönen E . Evaluation of genetic markers as instruments for mendelian randomization studies on vitamin D. PLoS One 2012; 7: e37465.
Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 2010; 376: 180–188.
Narvaez CJ, Matthews D, Broun E, Chan M, Welsh J . Lean phenotype and resistance to diet-induced obesity in vitamin D receptor knockout mice correlates with induction of uncoupling protein-1 in white adipose tissue. Endocrinology 2009; 150: 651–661.
Ochs-Balcom HM, Cicek MS, Thompson CL, Tucker TC, Elston RC, JP S et al. Association of vitamin D receptor gene variants, adiposity and colon cancer. Carcinogenesis 2008; 29: 1788–1793.
Ye WZ, Reis AF, Dubois-Laforgue D, Bellanne-Chantelot C, Timsit J, Velho G . Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset. Eur J Endocrinol 2001; 145: 181–186.
Barger-Lux MJ, Heaney RP, Hayes J, DeLuca HF, Johnson ML, Gong G . Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D receptor density. Calcif Tissue Int 1995; 57: 161–162.
Filus A, Trzmiel A, Kuliczkowska-Plaksej J, Tworowska U, Jedrzejuk D, Milewicz A et al. Relationship between vitamin D receptor BsmI and FokI polymorphisms and anthropometric and biochemical parameters describing metabolic syndrome. Aging Male 2008; 11: 134–139.
Tworowska-Bardzinska U, Lwow F, Kubicka E, Laczmanski L, Jedzrzejuk D, Dunajska K et al. The vitamin D receptor gene BsmI polymorphism is not associated with anthropometric and biochemical parameters describing metabolic syndrome in postmenopausal women. Gynecol Endocrinol 2008; 24: 514–518.
Ioannidis JP, Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG . Genetic associations in large versus small studies: an empirical assessment. Lancet 2003; 361: 567–571.
Jones G, Prosser DE . The activating enzymes of vitamin D metabolism (25- and 1alpha- hydroxylases). In: Feldman D, Pike JW, Adams JS, (eds) Vitamin D vol. 1. Elsevier Academic Press: London, UK; Waltham, MA, USA; San Diego, CA, USA, 2011. pp 23–42.
Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K . A comprehensive review of genetic association studies. Genet Med 2002; 4: 45–61.
Acknowledgements
We thank the Centre for Longitudinal studies, Institute of Education (original data producers) for providing the data. The Medical Research Council funded the 2002–2004 clinical follow-up of the 1958 birth cohort (grant G0000934). We also thank Ruth JF Loos for providing the summary results from the GIANT consortium. This work was undertaken at the Centre for Paediatric Epidemiology and Biostatistics, which benefits from funding support from the MRC in its capacity as the MRC Centre of Epidemiology for Child Health. Research at the University College London Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive. Funding for the project was provided by the British Heart Foundation (grant PG/09/023), Academy of Finland (project 139900), the PrevMetSyn/Salve project from Academy of Finland/MRC and the UK Medical Research Council (grant G0601653). Further support was obtained from the ENGAGE project and grant agreement HEALTH-F4-2007-201413.
Disclaimer
The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. JW is the Director of Statistical Genetics at GlaxoSmithKline. The company had no role in the production of the paper, development or interpretation of the study questions or in the decision to submit for publication.
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Vimaleswaran, K., Cavadino, A., Berry, D. et al. Genetic association analysis of vitamin D pathway with obesity traits. Int J Obes 37, 1399–1406 (2013). https://doi.org/10.1038/ijo.2013.6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2013.6
Keywords
This article is cited by
-
Association of CYP2R1 and CYP27B1 genes with the risk of obesity and vitamin D metabolism in Saudi women
Journal of Genetic Engineering and Biotechnology (2023)
-
BsmI gene polymorphism of vitamin D receptor in obese Egyptian male medical students and its relationship with vitamin D deficiency
Egyptian Journal of Medical Human Genetics (2022)
-
Association of vitamin D pathway genes polymorphisms with pulmonary tuberculosis susceptibility in a Chinese population
Genes & Nutrition (2021)
-
The association between vitamin D receptor polymorphisms and tissue-specific insulin resistance in human obesity
International Journal of Obesity (2021)
-
Genetic variants of VDR and CYP2R1 affect BMI independently of serum vitamin D concentrations
BMC Medical Genetics (2020)