Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: The DIABHYCAR prospective study

Ferrarezi, Daniela A.F.; Bellili-Muñoz, Naima; Dubois-Laforgue, D.; Cheurfa, Nadir; Lamri, Amel; Reis, AF; Feuvre, Claude Le; Roussel, Ronan; Fumeron, Frédéric; Timsit, José; Marre, Michel; Velho, Gilberto

doi:10.1016/j.diabet.2012.11.004

Cited by 41 publications

(31 citation statements)

References 39 publications

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“…Genetic studies involving DM nephropathy and related complications are not consistent in many aspects [ 31 – 34 ]. Some polymorphisms tested in this study were reported as being associated with type 1 DM ( IL12B rs3212227 [ 35 ], IL4R [ 36 , 37 ], IL13 [ 37 ], VDR rs1544410 [ 38 , 39 ], and VDR rs2228570 [ 38 ]), type 2 DM susceptibility ( VDR rs2228570 [ 40 ], VDR rs1544410 [ 41 ]), and phenotype of type 2 DM ( VDR rs2228570 [ 42 ], VDR rs1544410 [ 41 , 43 ]). VDR rs2228570 and IL4 polymorphisms were also related to the risk of chronic kidney disease [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

T-Cell Cytokine Gene Polymorphisms and Vitamin D Pathway Gene Polymorphisms in End-Stage Renal Disease due to Type 2 Diabetes Mellitus Nephropathy: Comparisons with Health Status and Other Main Causes of End-Stage Renal Disease

Grzegorzewska

Ostromecki²,

Zielińska

et al. 2014

Journal of Diabetes Research

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Background. T-cell cytokine gene polymorphisms and vitamin D pathway gene polymorphisms were evaluated as possibly associated with end-stage renal disease (ESRD) resulting from type 2 diabetes mellitus (DM) nephropathy. Methods. Studies were conducted among hemodialysis (HD) patients with ESRD due to type 2 DM nephropathy, chronic glomerulonephritis, chronic infective tubulointerstitial nephritis, and hypertensive nephropathy as well as in healthy subjects. A frequency distribution of T-cell-related interleukin (IL) genes (IL18 rs360719, IL12A rs568408, IL12B rs3212227, IL4R rs1805015, IL13 rs20541, IL28B rs8099917, IL28B, and rs12979860) and vitamin D pathway genes (GC genes: rs2298849, rs7041, and rs1155563; VDR genes: rs2228570, rs1544410; and RXRA genes: rs10776909, rs10881578, and rs749759) was compared between groups. Results. No significant differences in a frequency distribution of tested polymorphisms were shown between type 2 DM nephropathy patients and controls. A difference was found in IL18 rs360719 polymorphic distribution between the former group and chronic infective tubulointerstitial nephritic patients (P trend = 0.033), which also differed in this polymorphism from controls (P trend = 0.005). Conclusion. T-cell cytokine and vitamin D pathway gene polymorphisms are not associated with ESRD due to type 2 DM nephropathy in Polish HD patients. IL18 rs360719 is probably associated with the pathogenesis of chronic infective tubulointerstitial nephritis.

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Section: Discussionmentioning

confidence: 99%

T-Cell Cytokine Gene Polymorphisms and Vitamin D Pathway Gene Polymorphisms in End-Stage Renal Disease due to Type 2 Diabetes Mellitus Nephropathy: Comparisons with Health Status and Other Main Causes of End-Stage Renal Disease

Grzegorzewska

Ostromecki²,

Zielińska

et al. 2014

Journal of Diabetes Research

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“…This study was carried out in 41 Caucasian patients with documented CAD. Moreover, the DIABHYCAR prospective cohort study [37], including 3,137 patients with type 2 diabetes, also demonstrated an increased risk for incident cases of CAD among carriers of the B allele (hazard ratio = 1.16, 95% CI = 1.05-1.29, p = 0.002). Although the present meta-analysis did not find any associations between Fok I, Taq I, Bsm I, and Apa I polymorphisms of the VDR gene and the risk of CAD in the overall population, in Caucasians, and in Asians, the results should be interpreted with caution.…”

Section: Discussionmentioning

confidence: 99%

Common Variants of Vitamin D Receptor Gene Polymorphisms and Susceptibility to Coronary Artery Disease: A Systematic Review and Meta-Analysis

Alizadeh¹,

Djafarian²,

Alizadeh

et al. 2017

Lifestyle Genomics

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Background and Aims:ApaI, FokI, TaqI, and BsmI polymorphisms in the vitamin D receptor (VDR) gene have been reported to be associated with the risk of coronary artery disease (CAD), although the results of previous studies have been inconsistent. The aim of this study was to explore whether these polymorphisms play a role in the genetic susceptibility to CAD. Methods: A comprehensive search of Medline and Embase databases was conducted for studies evaluating the association between the VDR polymorphisms and CAD risk. Odds ratios with 95% confidence intervals were calculated to assess the strength of association in the dominant model, recessive model, allelic model, and genotypes contrast. Results: Nine studies involving a total of 5,259 cases and 1,981 controls were finally included in this meta-analysis. Overall, no significant associations were found between ApaI, FokI, TaqI, and BsmI polymorphisms and the risk of CAD in any of the genetic models (all p ˃ 0.05). Moreover, a subgroup analysis by ethnicity did not reveal a significant relationship between any of the examined polymorphisms and CAD risk in Caucasians and East-Asians for any model (all p ˃ 0.05). Conclusion: Current evidence suggests that the ApaI, FokI, TaqI, and BsmI polymorphisms of the VDR gene might not be associated with genetic susceptibility to CAD. Further well-designed studies with large sample sizes are needed to confirm our results.

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“…Finally, the VDR seems to modify cancer-related processes by regulating cell proliferation, differentiation, and apoptosis [ 16 , 17 ]. In line with this, the commonly studied VDR SNP FokI (in low LD with rs7968585) appears to be associated with T2D, at least in Asian populations [ 13 , 18 ] and cancer [ 44 , 45 ]; and the SNPs ApaI, BsmI, as well as TaqI appear to be associated with CAD [ 22 – 24 ] as well as with cancer [ 44 , 45 ] and cancer-related mortality [ 21 ]; and some Cdx2 (in low LD with rs7968585) haplotypes appear to be associated with increased risk of cancer [ 46 ]. However, in our study, none of the FokI, BsmI, TaqI, ApaI, Cdx2 SNPs showed any significant associations with the risk for these outcomes, which might be due to inter-population genetic variances.…”

Section: Discussionmentioning

confidence: 83%

Genetic Variations in the Vitamin D Receptor Predict Type 2 Diabetes and Myocardial Infarction in a Community-Based Population: The Tromsø Study

et al. 2015

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BackgroundThough the associations between low serum 25-hydroxyvitamin D (25(OH)D) levels and health outcomes such as type 2 diabetes (T2D), myocardial infarction (MI), cancer, and mortality are well-studied, the effect of supplementation with vitamin D is uncertain. This may be related to genetic differences. Thus, rs7968585, a single nucleotide polymorphism (SNP) of the vitamin D receptor (VDR), has recently been reported as a predictor of composite health outcome. We therefore aimed to evaluate whether rs7968585 predicts separate clinical outcomes such as T2D, MI, cancer, and mortality in a community-based Norwegian population.Methods and FindingsMeasurements and DNA were obtained from the participants in the Tromsø Study in 1994–1995, registered with the outcomes of interest and a randomly selected control group. The impact of the rs7968585 genotypes was evaluated with Cox proportional hazards. A total of 8,461 subjects were included among whom 1,054 subjects were registered with T2D, 2,287 with MI, 3,166 with cancer, and 4,336 with death. Mean follow-up time from birth was 60.8 years for T2D and MI, 61.2 years for cancer, while mean follow-up time from examination date was 16.5 years for survival. Mean serum 25(OH)D levels did not differ across the rs7968585 genotypes. With the major homozygote genotype as reference, the minor homozygote subjects had hazard ratios of 1.25 (95% CI 1.05–1.49) for T2D and 1.14 (1.02–1.28) for MI (P = 0.011 and 0.023, respectively, without the Bonferroni correction). No significant interaction between serum 25(OH)D status and the rs7968585 genotype was found for any of the endpoints.ConclusionsThe VDR-related SNP rs7968585 minor allele is a significant and positive predictor for T2D and possibly for MI. Since the functional mechanism of this SNP is not yet understood, and the association with T2D is reported for the first time, confirmatory studies are needed.

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Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: The DIABHYCAR prospective study

Cited by 41 publications

References 39 publications

T-Cell Cytokine Gene Polymorphisms and Vitamin D Pathway Gene Polymorphisms in End-Stage Renal Disease due to Type 2 Diabetes Mellitus Nephropathy: Comparisons with Health Status and Other Main Causes of End-Stage Renal Disease

T-Cell Cytokine Gene Polymorphisms and Vitamin D Pathway Gene Polymorphisms in End-Stage Renal Disease due to Type 2 Diabetes Mellitus Nephropathy: Comparisons with Health Status and Other Main Causes of End-Stage Renal Disease

Common Variants of Vitamin D Receptor Gene Polymorphisms and Susceptibility to Coronary Artery Disease: A Systematic Review and Meta-Analysis

Genetic Variations in the Vitamin D Receptor Predict Type 2 Diabetes and Myocardial Infarction in a Community-Based Population: The Tromsø Study

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