Genetic association analysis of vitamin D receptor gene polymorphisms and obesity-related phenotypes

Correa‐Rodríguez, María; Carrillo-Ávila, José Antonio; González‐Jiménez, Emilio; Vargas, Sofia; Martı́n, Javier; Rueda‐Medina, Blanca

doi:10.1016/j.gene.2017.10.029

Cited by 23 publications

(20 citation statements)

References 26 publications

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“…There are now studies that confirm both the positive and negative relationship. The Correa-Rodríguez M study in Spain conducted on Caucasian young adults population (58), Hasan et al (59) study on the Arab adults residing in the United Arab Emirates; Rahmadhani R in Malaysia (60), did not demonstrate a reliable association with obesity, but found association with the metabolic syndrome components, reduced vitamin D levels, insulin resistance (60), and Fokl and Bsml—with systolic blood pressure (59). Ruiz-Ojeda in the 1,020 review draws the following conclusions: obesity reported that associations with VDR polymorphisms could be related to either a direct effect of vitamin D in adipocyte differentiation and metabolism, or an indirect effect by modulation of insulin secretion (56).…”

Section: Mechanism Of Action Of Vitamin D In Obesitymentioning

confidence: 98%

Vitamin D Insufficiency in Overweight and Obese Children and Adolescents

et al. 2019

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Excessive body weight and obesity in childhood and adolescence are becoming more and more important unfavorable factors that entail extremely adverse consequences and require close attention of physicians of any specialty. Along with the high prevalence of obesity and metabolic syndrome in pediatric patients, children and adolescents in the majority of countries are diagnosed with vitamin D deficiency. Among the non-calcaemic effects of vitamin D, a significant role is played by its impact on the hormonal regulation of glucose metabolism and the synthesis of adipokines by fat tissue. The review presents literature data indicative of a close pathogenic relationship between vitamin D insufficiency and impaired tissue insulin sensitivity. It demonstrates the role of vitamin D insufficiency in immune reactions resulting in development of subclinical inflammation in fat tissue infiltrated with macrophages and lymphocytes. It also shows the role of adipokines, immune system cells and pro-inflammatory cytokines produced by them in the pathogenesis of obesity, as well as the function of vitamin D as an endocrine and paracrine regulator of the process of inflammation in adipose tissue. The relationships between the principal adipokines (leptin, adiponectin, resistin) are revealed in the presence of normal vitamin D content and in vitamin D deficiency. The carbohydrate and lipid metabolism parameters in overweight children and adolescents with vitamin D insufficiency are analyzed. A high prevalence of vitamin D insufficiency in overweight and obese children and adolescents (increasing along with the severity of obesity) is demonstrated. The review also presents the current recommendations for the correction of vitamin D insufficiency and underlines the need for higher cholecalciferol doses to achieve serum calcifediol targets in overweight and obese children and adolescents.

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Section: Mechanism Of Action Of Vitamin D In Obesitymentioning

confidence: 98%

Vitamin D Insufficiency in Overweight and Obese Children and Adolescents

et al. 2019

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“…Although the pathophysiological mechanisms underlying these associations remain unexplained, they could be related either to a direct effect of vitD on adipocyte differentiation and metabolism or to an indirect effect by modulation of insulin secretion. On the other hand, null associations between VDR SNPs and obesity have also been reported [39][40][41][42][43][44].…”

Section: Vdr Genetic Variantsmentioning

confidence: 99%

Genetic Factors and Molecular Mechanisms of Vitamin D and Obesity Relationship

et al. 2018

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Vitamin D (vitD) deficiency is associated with a wide range of chronic diseases and conditions, including obesity, and with an increasing severity of metabolic dysregulation, such as insulin resistance, hyperlipidemia, liver disease, and hypertension, both in children and adults. However, the nature of the association between low vitD status and obesity remains unclear. This fact has motivated the scientific community to conduct genetic association analyses between 25-hydroxyvitamin D (25[OH]D)-related genes and obesity traits. In this line, the variation in the vitD receptor (VDR) gene represents the bulk of the findings. Specifically, polymorphisms in the VDR gene have been associated with obesity traits in some but not all, studies. Thus, results regarding this matter remain inconclusive. Other genes aside from VDR have also been investigated in relation to obesity-related traits. However, again, findings have been inconsistent. In general, results point to the fact that the DBP/GC gene could be an important protein-linking obesity and vitD status. On the other hand, several studies have attempted to determine the molecular mechanism of the relationship between 25(OH)-D levels and obesity. Some of these studies suggest that vitD, due to its fat-soluble characteristic, is retained by the adipose tissue and has the capacity to metabolize 25(OH)-D locally, and this can be altered during obesity. Additionally, vitD is capable of regulating the gene expression related to adipogenesis process, inflammation, oxidative stress, and metabolism in mature adipocytes. Therefore, the aim of the present review was to evaluate the association between obesity and vitD deficiency describing the main molecular mechanism of the relationship and the link with genetic factors. Key Messages: Low serum 25(OH)-D is positively associated with obesity or BMI in adults and children. Circulating vitD concentrations are, at least, partially determined by genetic factors. VitD plays an important role in the adipogenesis process and inflammation status in adipocytes and adipose tissue.

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“…In a study of Egyptian patients with T2DM, an analysis of some polymorphisms in the VDR ( Fok I and Bsm I) found that the genotype TT for the Fok I SNP was associated with lower 25(OH)D levels and higher waist circumference as well as worse metabolic profiles than were FF genotypes . Yet another study in 701 healthy young adults in Spain concluded that VDR polymorphisms were not associated with obesity, because Fok I, Taq I and Bsm I SNPs did not correlate with percentage fat mass or body weight after correcting for multiple testing . Bi‐directional Mendelian randomization methods have also been used to explore the relationship between vitamin D and obesity.…”

Section: Vitamin D and Obesitymentioning

confidence: 99%

Vitamin D and cardiometabolic disorders: a review of current evidence, genetic determinants and pathomechanisms

2018

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Vitamin D deficiency has been implicated in the pathophysiology of cardiometabolic disorders including obesity, type 2 diabetes mellitus, cardiovascular diseases and polycystic ovary syndrome. Despite a large number of experimental and observational studies supporting a role for vitamin D in these pathologies, randomized controlled trials have reported little to no effect of vitamin D supplementation in the prevention or treatment of these disorders, although some results remain ambiguous. Polymorphisms in genes related to vitamin D metabolism, particularly in the vitamin D receptor and binding protein and the metabolizing enzyme 1-α-hydroxylase, have emerged as potential contributors to these divergent results. It is now becoming increasingly recognized that the effects and potential benefits of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity and/or the presence of genetic variants, which affect individual responses to supplementation. However, these factors have seldom been explored in the available literature. Future trials should consider inter-individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of cardiometabolic health.

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Genetic association analysis of vitamin D receptor gene polymorphisms and obesity-related phenotypes

Cited by 23 publications

References 26 publications

Vitamin D Insufficiency in Overweight and Obese Children and Adolescents

Vitamin D Insufficiency in Overweight and Obese Children and Adolescents

Genetic Factors and Molecular Mechanisms of Vitamin D and Obesity Relationship

Vitamin D and cardiometabolic disorders: a review of current evidence, genetic determinants and pathomechanisms

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