Role of gene polymorphisms in vitamin D metabolism and in multiple sclerosis

Karahalıl, Bensu

doi:10.2478/aiht-2018-69-3065

Cited by 10 publications

(5 citation statements)

References 41 publications

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“…Moreover, our genetic models' analysis results showed a significant association under three models (dominant, recessive, and codominant) OR > 1, the strongest impact was for homozygous codominant which may emphasize the potential role of GG genotypes as a risk factor for developing MS. These findings come in agreement with previous studies which showed that a decrease in the concentration of vitamin D in patients with MS was associated with the presence of genetic changes, most notably at rs7041 in the DBP gene [16,33] and can be explained that genetic polymorphisms cause low concentration of vitamin D levels and increase susceptibility to develop MS [34][35][36].…”

Section: Discussionsupporting

confidence: 93%

Assessment of vitamin D-binding protein (DBP) gene polymorphisms and their correlation with multiple sclerosis: a case-control study in a sample of the Syrian population

Alhomsi

Aboualchamat

Alkadi

2020

Egypt J Med Hum Genet

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Background Vitamin D deficiency is a major health concern as it increases the risk of developing many serious diseases. Recently, the correlation between vitamin D deficiency and multiple sclerosis (MS) is a matter of serious debate. In this case-control study, we aimed to assess the correlation between genetic changes in the vitamin D-binding protein (DBP) gene and their consequence on MS patients. Our sample study consisted of 110 individuals; 40 patients with MS as cases and 70 healthy controls. Vitamin D levels were determined by immunofluorescence assay, and polymorphisms at rs7041 (c.1296 T > G p.Asp416Glu) and rs4588 (c.1307C > A p.Thr420Lys) of the DBP gene were genotyped using PCR/RFLP method for all cases and controls. Results Our results showed that genotype frequencies were consistent with Hardy-Weinberg equilibrium. A significant association was found in rs7041 (c.1296TT) homozygous wild-type, and the odds ratio was < 1 suggesting a protective role against developing MS (OR; 0.03, p = 0.0002) whereas the c.1296GG genotype was significantly correlated with an increased risk for MS by 6 folds (OR: 6.0000, p < 0.0001). No significant association was noted at rs4588 and MS occurrence. In addition, our compound genotyping results revealed that haplotypes 1S-1S are 6 times more likely to develop MS, whereas haplotypes 1F-1F had a more protective role in MS patients (OR: 0.063, p = 0.06.), respectively. The risk of vitamin D insufficiency in patients was greater by 14 folds compared to controls (OR: 14.05, p = 0.0128). Furthermore, the c.1296GG genotype was associated significantly by more than 4 times with insufficient levels of vitamin D and by 7 folds with vitamin deficiency. Conclusions We conclude that polymorphisms in the DBP gene could have independent effects on the risk of developing multiple sclerosis. The homozygous recessive genotype at rs7041 was associated with insufficient levels of vitamin D and with the risk of MS emergence.

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Section: Discussionsupporting

confidence: 93%

Assessment of vitamin D-binding protein (DBP) gene polymorphisms and their correlation with multiple sclerosis: a case-control study in a sample of the Syrian population

Alhomsi

Aboualchamat

Alkadi

2020

Egypt J Med Hum Genet

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“…Growing evidence suggests that vitamin D is an environmental factor significantly affecting MS prevalence that is closely associated with the latitudinal gradient, where an increased exposure to UVB stimulates the cutaneous production of vitamin D reducing the risk of disease [71,72]. Accordingly, low levels of 25(OH)D, in association with the presence of genetic polymorphisms involving the metabolism of vitamin D, imply a greater risk of developing MS [73][74][75]. In addition, it has been observed that the presence of gene variants of the CYP27B1 seems to increase the risk and activity of MS [76][77][78].…”

Section: Multiple Sclerosismentioning

confidence: 99%

The role of vitamin D in autoimmune diseases: could sex make the difference?

et al. 2021

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Over the last decades, a central role for vitamin D in immune modulation has been well established. The active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with vitamin D receptor, exerts different activities on the innate and adaptive immune system, among which suppression of inflammation and promotion of tolerogenic responses. Vitamin D insufficiency has been linked to autoimmune disorders that commonly display significant differences between females and males due to genetic, epigenetic, hormonal, and environmental factors. Notably, a number of studies recently showed a cross-talk between vitamin D and the sex hormone estrogen. Estrogen-mediated effects on immune response may favor a Th1 profile or a Th2 profile, depending on hormone concentration. Thus, estrogen-mediated effects appear to be variable on autoimmunity depending on its concentration but also on the pathogenic mechanisms underlying the different autoimmune diseases (i.e., Th1- or Th2-mediated diseases). Notably, estrogen has been demonstrated to enhance vitamin D function favoring its accumulation, and increasing the expression of vitamin D receptor, thus resulting in a more potent anti-inflammatory response in females than males. On the other hand, vitamin D has been shown to downregulate in immune cells the expression of aromatase, which converts testosterone to estrogen, leading to a decrease in estrogen level. Overall, available data allow us to hypothesize a higher protective effect of vitamin D-based therapeutic approaches in women, at least in fertile age, than in men. Future studies are needed to expand current knowledge on the immunomodulatory role of vitamin D in a sex and gender perspective, paving the way to a more personalized therapeutic approach in autoimmune diseases.

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“…Additionally, vitamin D can modulate both adaptive and innate immunity [ 191 ]. Indeed, vitamin D deficiency is associated with several autoimmune diseases [ 192 ], for example, rheumatoid arthritis (RA) [ 193 , 194 ], inflammatory bowel disease (IBD) [ 195 , 196 , 197 , 198 ] and multiple sclerosis (MS) [ 199 , 200 , 201 , 202 ]. Associations between low vitamin D status and autoimmune thyroid diseases and thyroid cancer were also found [ 203 ].…”

Section: Vitamin D: State Of the Artmentioning

confidence: 99%

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

Riccardi

Perrone

Napolitano

et al. 2020

Cancers

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Vitamin D is a fat-soluble steroid hormone playing a pivotal role in calcium and phosphate homeostasis as well as in bone health. Vitamin D levels are not exclusively dependent on food intake. Indeed, the endogenous production—occurring in the skin and dependent on sun exposure—contributes to the majority amount of vitamin D present in the body. Since vitamin D receptors (VDRs) are ubiquitous and drive the expression of hundreds of genes, the interest in vitamin D has tremendously grown and its role in different diseases has been extensively studied. Several investigations indicated that vitamin D action extends far beyond bone health and calcium metabolism, showing broad effects on a variety of critical illnesses, including cancer, infections, cardiovascular and autoimmune diseases. Epidemiological studies indicated that low circulating vitamin D levels inversely correlate with cutaneous manifestations and bone abnormalities, clinical hallmarks of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumour predisposition syndrome causing significant pain and morbidity, for which limited treatment options are available. In this context, vitamin D or its analogues have been used to treat both skin and bone lesions in NF1 patients, alone or combined with other therapeutic agents. Here we provide an overview of vitamin D, its characteristic nutritional properties relevant for health benefits and its role in NF1 disorder. We focus on preclinical and clinical studies that demonstrated the clinical correlation between vitamin D status and NF1 disease, thus providing important insights into disease pathogenesis and new opportunities for targeted therapy.

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Role of gene polymorphisms in vitamin D metabolism and in multiple sclerosis

Cited by 10 publications

References 41 publications

Assessment of vitamin D-binding protein (DBP) gene polymorphisms and their correlation with multiple sclerosis: a case-control study in a sample of the Syrian population

Assessment of vitamin D-binding protein (DBP) gene polymorphisms and their correlation with multiple sclerosis: a case-control study in a sample of the Syrian population

The role of vitamin D in autoimmune diseases: could sex make the difference?

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

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