Contribution of VDR polymorphisms to type 1 diabetes susceptibility: Systematic review of case–control studies and meta-analysis

Tizaoui, Kalthoum; Kaabachi, Wajih; Hamzaoui, A.; Hamzaoui, Kamel

doi:10.1016/j.jsbmb.2014.03.011

Cited by 53 publications

(52 citation statements)

References 63 publications

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“…Ogunkalade et al demonstrated that VDR expression did determine insulin secretory capacity in a functional study [51]. While direct action on the pancreas has been postulated, this SNP has not been demonstrated to be associated with an increased susceptibility to type 1 diabetes mellitus on its own [52]. Although studies on BsmI suggested an association with type 2 diabetes mellitus, a consequence of insulin resistance, this was not reflected by meta-analyses as many of these studies were of small sample sizes [53, 54].…”

Section: Discussionmentioning

confidence: 99%

The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency, obesity and insulin resistance in adolescents residing in a tropical country

et al. 2017

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BackgroundThe vitamin D receptor (VDR) gene is expressed abundantly in different tissues; including adipocytes and pancreatic beta cells. The rs1544410 or BsmI single nucleotide polymorphism (SNP) in the intronic region of the VDR gene has been previously associated with vitamin D levels, obesity and insulin resistance.AimsThis study was aimed to examine the association between BsmI polymorphism and risk of vitamin D deficiency, obesity and insulin resistance in adolescents living in a tropical country.MethodsThirteen-year-old adolescents were recruited via multistage sampling from twenty-three randomly selected schools across the city of Kuala Lumpur, Malaysia (n = 941). Anthropometric measurements were obtained. Obesity was defined as body mass index higher than the 95th percentile of the WHO chart. Levels of fasting serum vitamin D (25-hydroxyvitamin D (25(OH)D)), glucose and insulin were measured. HOMA-IR was calculated as an indicator for insulin resistance. Genotyping was performed using the Sequenom MassARRAY platform (n = 807). The associations between BsmI and vitamin D, anthropometric parameters and HOMA-IR were examined using analysis of covariance and logistic regression.ResultThose with AA genotype of BsmI had significantly lower levels of 25(OH)D (p = 0.001) compared to other genotypes. No significant differences was found across genotypes for obesity parameters. The AA genotype was associated with higher risk of vitamin D deficiency (p = 0.03) and insulin resistance (p = 0.03) compared to GG. The A allele was significantly associated with increased risk of vitamin D deficiency compared to G allele (adjusted odds ratio (OR) = 1.63 (95% Confidence Interval (CI) 1.03–2.59, p = 0.04). In those with concurrent vitamin D deficiency, having an A allele significantly increased their risk of having insulin resistance compared to G allele (adjusted OR = 2.66 (95% CI 1.36–5.19, p = 0.004).ConclusionVDR BsmI polymorphism was significantly associated with vitamin D deficiency and insulin resistance, but not with obesity in this population.

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Section: Discussionmentioning

confidence: 99%

The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency, obesity and insulin resistance in adolescents residing in a tropical country

et al. 2017

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“…Eight out of nine meta-analyses on the VDR gene and T1D published between 2006 and 2017 agree on the conclusion that rs10735810 ( FokI ) and/or rs1544410 ( BsmI ) SNPs play an important role in the development of T1D [76,77,78,79,80,81,82,83] (Table 3). …”

Section: Vitamin D Pathwaysmentioning

confidence: 92%

“…To date, there are 65 publications [19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83] on the association of VDR gene SNPs in T1D: these include case-control datasets [20,22,23,25,26,27,28,…”

Section: Vitamin D Pathwaysmentioning

confidence: 99%

“…On the basis of the diverging results of VDR SNPs and T1D susceptibility, nine meta-analyses have been performed [75,76,77,78,79,80,81,82,83]. Eight out of nine meta-analyses on the VDR gene and T1D published between 2006 and 2017 agree on the conclusion that rs10735810 ( FokI ) and/or rs1544410 ( BsmI ) SNPs play an important role in the development of T1D [76,77,78,79,80,81,82,83] (Table 3).…”

Section: Vitamin D Pathwaysmentioning

confidence: 99%

“…Interestingly, the regional stratification analysis indicates that the rs1544410 ( BsmI ) “B” allele conferred an enhanced T1D risk in East Asia but the rs10735810 ( FokI ) allele “F” in the West Asian population. An additional meta-analysis covering the four VDR SNPs in Asian, European and Latino populations concluded that “BAT” was a significant T1D risk factor [81]. Furthermore, a recent meta-analysis on the basis of nine studies comprising 1053 children with T1D (Asian, European and Latino origin) confirmed the “BB”genotype of rs1544410 ( BsmI ) as risk marker for T1D and also for the “tt” genotype of the rs731236 ( TaqI ) SNP [83].…”

Section: Vitamin D Pathwaysmentioning

confidence: 99%

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Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition

Penna-Martinez

Badenhoop

2017

Genes

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The etiology and pathophysiology of type 1 diabetes remain largely elusive with no established concepts for a causal therapy. Efforts to clarify genetic susceptibility and screening for environmental factors have identified the vitamin D system as a contributory pathway that is potentially correctable. This review aims at compiling all genetic studies addressing the vitamin D system in type 1 diabetes. Herein, association studies with case control cohorts are presented as well as family investigations with transmission tests, meta-analyses and intervention trials. Additionally, rare examples of inborn errors of vitamin D metabolism manifesting with type 1 diabetes and their immune status are discussed. We find a majority of association studies confirming a predisposing role for vitamin D receptor (VDR) polymorphisms and those of the vitamin D metabolism, particularly the CYP27B1 gene encoding the main enzyme for vitamin D activation. Associations, however, are tenuous in relation to the ethnic background of the studied populations. Intervention trials identify the specific requirements of adequate vitamin D doses to achieve vitamin D sufficiency. Preliminary evidence suggests that doses may need to be individualized in order to achieve target effects due to pharmacogenomic variation.

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Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

et al. 2020

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Regulation of immune function continues to be one of the most well-recognized extraskeletal actions of vitamin D. This stemmed initially from the discovery that antigen presenting cells such as macrophages could actively metabolize precursor 25-hydroxyvitamin D (25D) to active 1,25-dihydroxyvitamin D (1,25D). Parallel observation that activated cells from the immune system expressed the intracellular vitamin D receptor (VDR) for 1,25D suggested a potential role for vitamin D as a localized endogenous modulator of immune function. Subsequent studies have expanded our understanding of how vitamin D exerts effects on both the innate and adaptive arms of the immune system. At an innate level, intracrine synthesis of 1,25D by macrophages and dendritic cells stimulates expression of antimicrobial proteins such as cathelicidin, as well as lowering intracellular iron concentrations via suppression of hepcidin. By potently enhancing autophagy, 1,25D may also play an important role in combatting intracellular pathogens such as M. tuberculosis and viral infections. Local synthesis of 1,25D by macrophages and dendritic cells also appears to play a pivotal role in mediating T-cell responses to vitamin D, leading to suppression of inflammatory T helper (Th)1 and Th17 cells, and concomitant induction of immunotolerogenic Tregulatory responses. The aim of this review is to provide an update on our current understanding of these prominent immune actions of vitamin D, as well as highlighting new, less well-recognized immune effects of vitamin D. The review also aims to place this mechanistic basis for the link between vitamin D and immunity with studies in vivo that have explored a role for vitamin D supplementation as a strategy for improved immune health. This has gained prominence in recent months with the global coronavirus disease 2019 health crisis and highlights important new objectives for future studies of vitamin D and immune function.

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Contribution of VDR polymorphisms to type 1 diabetes susceptibility: Systematic review of case–control studies and meta-analysis

Cited by 53 publications

References 63 publications

The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency, obesity and insulin resistance in adolescents residing in a tropical country

The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency, obesity and insulin resistance in adolescents residing in a tropical country

Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition

Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

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