Abstract
Objective
One of the systemic infections is Brucellosis which is caused by facultative intracellular bacteria of the genus Brucella. Vitamin D is a fat-soluble prohormone, that metabolizes enzymes and its intracellular receptor creates the active hormone and also mediate in responses of immune system.
Methods
Current research consists of 102 patients with brucellosis who were selected based on culture, PCR results serology, and clinical symptoms. The control group composed of 102 healthy people. The polymorphism of genes (Bsm I, Fok I, Taq I, Apa I) encoding Vitamin D receptor (VDR) were assessed by the PCR-RFLP method.
Results
The results showed that ff, tt, aa, and bb genotypes in Fok I, ApaI, TaqI, and BsmI were significant in case/control groups (P-value ≤ 0.0001). The genotype frequency AA in the control group is higher than that of the study group, while genotype frequency aa in the study group is more than the control. The odds ratio for brucellosis in individuals with ff genotype is 37 times higher than that of Ff genotype. Also, the odds ratio of brucellosis in individuals with genotype tt, aa, and bb was 12, 53, and 6 times higher than those of the Aa, Bb, and Tt genotypes.
Conclusion
The genotypes aa and ff in the positions of the ApaI and FokI are of higher importance. The brucellosis risk in individuals accompanied aa genotype at Apa I is 53 times higher than that of the genotype AA, in other words, AA and BB, TT and FF genotypes are protective against the disease.
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Data availability
The data presented in this study are available on request from the corresponding author.
References
Pappas G, Papadimitriou P, Akritidis N, Christou L, Tsianos EV (2006) The new global map of human brucellosis. Lancet Infect Dis 6(2):91–99
Paradise LJ, Friedman H, Bendinelli M (2006) Opportunistic intracellular bacteria and immunity. Springer, New York
Ko J, Gendron-Fitzpatrick A, Splitter GA (2002) Susceptibility of IFN regulatory factor-1 and IFN consensus sequence binding protein-deficient mice to brucellosis. J Immunol 168(5):2433–2440
Keramat F, Alikhani MY, Poorolajal J, Akbari S (2018) Comparison of serum level of 25 (OH) vitamin D3 in brucellosis patients with healthy persons in Hamadan, West of Iran. J Infect Dev Ctries 12(06):448–53
Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M (2008) Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics 122(2):398–417
Svensson D, Nebel D, Nilsson B-O (2016) Vitamin D3 modulates the innate immune response through regulation of the hCAP-18/LL-37 gene expression and cytokine production. Inflamm Res 65(1):25–32
Kamen DL, Tangpricha V (2010) Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med 88(5):441–450
Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J (2015) Harrison’s principles of internal medicine, 19e. Mcgraw-hill, New York
Gul H, Erdem H (2015) Brucellosis (Brucella Species). In: Mandell G, Bennett J, Dolin R (eds) Principles and practice of infectious disease. Elsevier;, New York
Ruiz-Ballesteros AI, Meza-Meza MR, Vizmanos-Lamotte B, Parra-Rojas I, de la Cruz-Mosso U (2020) Association of vitamin D metabolism gene polymorphisms with autoimmunity: evidence in population genetic studies. Int J Mol Sci 21(24):9626
Makoui MH, Imani D, Motallebnezhad M, Azimi M, Razi B (2020) Vitamin D receptor gene polymorphism and susceptibility to asthma: meta-analysis based on 17 case-control studies. Ann Allergy Asthma Immunol 124(1):57–69
Mahmoudi H, Arabestani MR, Mousavi SF, Alikhani MY (2017) Molecular analysis of the coagulase gene in clinical and nasal carrier isolates of methicillin-resistant Staphylococcus aureus by restriction fragment length polymorphism. J global Antimicrob Resist 8:41–45
MWer S, Dykes D, Polesky H (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16(3):1215
Lins T, Nogueira LR, Lima RM, Gentil P, Oliveira RJd, Pereira RW (2007) A multiplex single-base extension protocol for genotyping Cdx2, FokI, BsmI, ApaI, and TaqI polymorphisms of the vitamin D receptor gene. Genet Mol Res 6(2):316–324
Cyprian F, Lefkou E, Varoudi K, Girardi G (2019) Immunomodulatory effects of vitamin D in pregnancy and beyond. Front Immunol 10:2739
Alhassan Mohammed H, Mirshafiey A, Vahedi H, Hemmasi G, Moussavi Nasl Khameneh A, Parastouei K et al (2017) Immunoregulation of inflammatory and inhibitory cytokines by vitamin D3 in patients with inflammatory bowel diseases. Scand J Immunol 85(6):386–394
Cantorna MT, Snyder L, Lin Y-D, Yang L (2015) Vitamin D and 1, 25 (OH) 2D regulation of T cells. Nutrients 7(4):3011–3021
Konya V, Czarnewski P, Forkel M, Rao A, Kokkinou E, Villablanca EJ et al (2018) Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells. J Allergy Clin Immunol 141(1):279–292
Penna G, Adorini L (2000) 1α, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 164(5):2405–2411
Coleman LA, Mishina M, Thompson M, Spencer SM, Reber AJ, Davis WG et al (2016) Age, serum 25-hydroxyvitamin D and vitamin D receptor (VDR) expression and function in peripheral blood mononuclear cells. Oncotarget 7(24):35512
Zhang K, Song L (2014) Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies. PLoS ONE 9(4):e96125
Zeljic K, Supic G, Stamenkovic Radak M, Jovic N, Kozomara R, Magic Z (2012) Vitamin D receptor, CYP27B1 and CYP24A1 genes polymorphisms association with oral cancer risk and survival. J Oral Pathol Med 41(10):779–787
Pani MA, Seissler J, Usadel K-H, Badenhoop K (2002) Vitamin D receptor genotype is associated with Addison’s disease. Eur J Endocrinol 147(5):635–640
Dankers W, Colin EM, Van Hamburg JP, Lubberts E (2017) Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol 7:697
Giannini S, Giusti A, Minisola S, Napoli N, Passeri G, Rossini M et al (2022) The immunologic profile of Vitamin D and its role in different immune-mediated diseases: an expert opinion. Nutrients 14(3):473
Mostowska A, Sajdak S, Pawlik P, Lianeri M, Jagodzinski PP (2013) Vitamin D receptor gene bsm I and Fok I polymorphisms in relation to ovarian cancer risk in the Polish population. Genetic Test Mol Biomark 17(3):183–187
Wilbur AK, Kubatko LS, Hurtado AM, Hill KR, Stone AC (2007) Vitamin D receptor gene polymorphisms and susceptibility M. tuberculosis in native Paraguayans. Tuberculosis 87(4):329–337
Nicolaidou P, Papadopoulou A, Matsinos Y, Georgouli H, Fretzayas A, Papadimitriou A et al (2007) Vitamin D receptor polymorphisms in hypocalcemic vitamin D-resistant rickets carriers. Hormone Res Paediatr 67(4):179–183
Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV et al (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367(6460):284–287
Divanoglou N, Komninou D, Stea EA, Argiriou A, Papatzikas G, Tsakalof A, Pazaitou-Panayiotou K, Georgakis MK, Petridou E (2021) Association of vitamin D receptor gene polymorphisms with serum vitamin D levels in a greek rural population (Velestino study). Lifestyle Genomics 14(3):81–90
Orton SM, Morris AP, Herrera BM, Ramagopalan SV, Lincoln MR, Chao MJ, Vieth R, Sadovnick AD (2008) Ebers GC evidence for genetic regulation of vitamin D status in twins with multiple sclerosis. Am J Clin Nutr 88(2):441–7
TajikN Jafari M, Nasiri MR, Mousavi T, Farnia P, Salek MAR (2009) The study of the association between vitamin D receptor common genetic polymorphisms and susceptibility to pulmonary tuberculosis. Razi J Med Sci 1(20):20–21
Acknowledgements
The authors wish to express their appreciation to the Vice-Chancellor of Research and Technology of Hamadan University of Medical Sciences, Hamadan, Iran. We also sincerely thank Professor Ali Reza Soltanian, Department of Biostatistics, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran, for his help in data analysis.
Funding
This study was granted by the Vice-Chancellor of Research and Technology of Hamadan University of Medical Sciences, Hamadan, Iran (Grant No: 9603302218).
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MYA and FK cooperated in the design of the study and selecting the patients. HM and YM contributed to sampling and data analysis. MYA and AK prepared the first draft. MYA and MS contributed to preparing and revising the manuscript. MYA and HM contributed to revising the manuscript. All authors have read and agreed to the published version of the manuscript.
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The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Hamadan University of Medical Sciences, Hamadan, Iran (IR.UMSHA.REC.1396.266).
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Informed consent was obtained from all subjects involved in the study.
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Mahmoudi, H., keramat, F., Saidijam, M. et al. Polymorphisms in vitamin D receptor genes and its relation with susceptibility to brucellosis: a case-control study. Mol Biol Rep 50, 2077–2083 (2023). https://doi.org/10.1007/s11033-022-08195-2
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DOI: https://doi.org/10.1007/s11033-022-08195-2