Genetic Variants in the Vitamin D Receptor Gene Increase the Risk of Urinary Tract Infection in a Southeast Population of Iran: A Case-control Study
Journal of Pediatric Nephrology,
Vol. 12 No. 1 (2024),
10 April 2025
https://doi.org/10.22037/jpn.v12i1.46226
Abstract
Background and Aim: Urinary tract infection (UTI) is a common infection affecting
children. Besides microorganism pathogens, genetic background plays a pivotal role in the
pathogenesis of diseases. Vitamin D receptor (VDR) plays a crucial role in the pathogenesis
of some cancers and infectious diseases. This study aimed to evaluate the association between
polymorphisms in the VDR gene and risk of UTI.
Methods: In the current study, 127 children affected by UTI were referred to the pediatric
nephrology clinic in Zahedan, and 100 subjects with no history of infection were genotyped.
The genotyping was carried out by restriction fragment length polymorphism-polymerase
chain reaction (RFLP-PCR). SPSS software, version 22.0 was used for statistical analysis.
Results: The results revealed that rs2228570C>T (FokI), rs7975232A>C (ApaI), and
rs731236T>C (TaqI) increased the risk of UTI, whereas rs1544410G>A (BsmI) decreased
the risk of the disease.
Conclusion: The results suggest that the genetic variants in the VDR gene may play a role in
the pathogenesis of UTI.
- Urinary tract infection
- Vitamin D
- vitamin D receptor
- single nucleotide polymorphism
How to Cite
References
[1] Odongo I, Ssemambo R, Kungu JM. Prevalence of escherichia
coli and its antimicrobial susceptibility profiles
among patients with UTI at Mulago Hospital, Kampala,
Uganda. Interdiscip Perspect Infect Dis. 2020; 2020:8042540.
[DOI:10.1155/2020/8042540] [PMID]
[2] Korbel L, Howell M, Spencer JD. The clinical diagnosis and
management of urinary tract infections in children and adolescents.
Paediatr Int Child Health. 2017; 37(4):273-9. [DOI:10.
1080/20469047.2017.1382046] [PMID]
[3] Mahyar A, Ayazi P, Sarkhosh Afshar A, Naserpour Farivar
T, Sahmani M, Oveisi S, et al. Vitamin D receptor gene
(FokI, TaqI, BsmI, and ApaI) polymorphisms in children
with urinary tract infection. Pediatr Res. 2018; 84(4):527-32.
[DOI:10.1038/s41390-018-0092-y] [PMID]
[4] Sadeghi-Bojd S, Hashemi M. Hypercalciuria and recurrent
urinary tract infections among children in Zahedan, Iran. J
Pak Med Assoc. 2008; 58(11):624-6. [PMID]
[5] Kaur R, Kaur R. Symptoms, risk factors, diagnosis and
treatment of urinary tract infections. Postgrad Med J. 2021;
97(1154):803-12. [DOI:10.1136/postgradmedj-2020-139090]
[PMID]
[6] Ayazi P, Mahyar A, Jahani HH, Daneshi MM, Karimzadeh
T, Salimi F. [Comparison of procalcitonin and C-reactive protein
tests in children with urinary tract infection (Persian)].
Iran J Pediatr 2009; 19(4):38-6. [Link]
[7] Hussein A, Askar E, Badawy A, Saad K, Zahran A, Elderwy
AA. Impact of cytokine genetic polymorphisms on the risk of
renal parenchymal infection in children. J Pediatr Urol. 2017;
13(6):593.e1-10. [DOI:10.1016/j.jpurol.2017.05.025] [PMID]
[8] Aslan S, Akil I, Aslan G, Onay H, Ozyurt BC, Ozkinay F.
Vitamin D receptor gene polymorphism in children with
urinary tract infection. Pediatr Nephrol. 2012; 27(3):417-21.
[DOI:10.1007/s00467-011-2000-0] [PMID]
[9] Junaid K, Rehman A. Impact of vitamin D on infectious
disease-tuberculosis-a review. Clin Nutr Exp. 2019; 25:1-10.
[DOI:10.1016/j.yclnex.2019.02.003]
[10] Hussein MM, Mohamed EM, Kamal TM, Deraz TE. Increased
susceptibility to complicated pneumonia among
egyptian children with FokI (rs2228570), not TaqI (rs731236),
vitamin D receptor gene polymorphism in association with
vitamin D deficiency: A case-control study. BMC Pediatr.
2023; 23(1):394. [DOI:10.1186/s12887-023-04192-x] [PMID]
[11] Dusso A, Brown AJ, Slatopolsky E. Vitamin D. Am J
Physiol Renal Physiol. 2005; 289(1):F8-28. [DOI:10.1152/ajprenal.
00336.2004] [PMID]
[12] Jahnukainen T, Chen M, Celsi G. Mechanisms of renal
damage owing to infection. Pediatr Nephrol. 2005; 20(8):1043-
53. [DOI:10.1007/s00467-005-1898-5] [PMID]
[13] White JH. Vitamin D signaling, infectious diseases, and regulation
of innate immunity. Infect Immun. 2008; 76(9):3837-
43. [DOI:10.1128/IAI.00353-08] [PMID]
[14] Zasloff M. Antimicrobial peptides, innate immunity, and
the normally sterile urinary tract. J Am Soc Nephrol. 2007;
18(11):2810-6. [DOI:10.1681/ASN.2007050611] [PMID]
[15] Equils O, Naiki Y, Shapiro A, Michelsen K, Lu D, Adams
J, et al. 1, 25-Dihydroxyvitamin D3 inhibits lipopolysaccharide-
induced immune activation in human endothelial cells.
Clin Exp Immunol. 2006; 143(1):58-64. [DOI:10.1111/j.1365-
2249.2005.02961.x] [PMID]
[16] Shalaby SA, Handoka NM, Amin RE. Vitamin D deficiency
is associated with urinary tract infection in children. Arch
Med Sci. 2018; 14(1):115-21. [DOI:10.5114/aoms.2016.63262]
[PMID]
[17] Tekin M, Konca C, Celik V, Almis H, Kahramaner Z, Erdemir
A, et al. The association between vitamin D levels and
urinary tract infection in children. Horm Res Paediatr. 2015;
83(3):198-203. [DOI:10.1159/000370046] [PMID]
[18] Mahyar A, Ayazi P, Safari S, Dalirani R, Javadi A, Esmaeily
S. Association between vitamin D and urinary tract infection
in children. Korean J Pediatr. 2018; 61(3):90-4. [DOI:10.3345/
kjp.2018.61.3.90] [PMID]
[19] A’t Hoen L, Bogaert G, Radmayr C, Dogan HS, Nijman RJ,
Quaedackers J, et al. Update of the EAU/ESPU guidelines
on urinary tract infections in children. J Pediatr Urol. 2021;
17(2):200-7. [DOI:10.1016/j.jpurol.2021.01.037] [PMID]
[20] ClicCalc. Sample size calculator. Determines the minimum
number of subjects for adequate study power [Internet].2025 [
Update 2025 December 19]. Available from: [Link]
[21] Nasiri H, Forouzandeh M, Rasaee MJ, Rahbarizadeh
F. Modified salting‐out method: High‐yield, high‐quality
genomic DNA extraction from whole blood using laundry
detergent. J Clin Lab Anal. 2005; 19(6):229-32. [DOI:10.1002/
jcla.20083] [PMID]
[22] Moore DD, Kato S, Xie W, Mangelsdorf DJ, Schmidt DR,
Xiao R, et al. The NR1H and NR1I receptors: Constitutive androstane
receptor, pregnene X receptor, farnesoid X receptor
alpha, farnesoid X receptor beta, liver X receptor alpha, liver
X receptor beta, and vitamin D receptor. Pharmacol Rev. 2006;
58(4):742-59. [DOI:10.1124/pr.58.4.6] [PMID]
[23] Bahrami A, Sadeghnia HR, Tabatabaeizadeh SA, Bahrami‐
Taghanaki H, Behboodi N, Esmaeili H, et al. Genetic and
epigenetic factors influencing vitamin D status. J Cell Physiol.
2018; 233(5):4033-43. [DOI:10.1002/jcp.26216] [PMID]
[24] Lang PO, Aspinall R. Vitamin D status and the host resistance
to infections: what it is currently (not) understood. Clin
Ther. 2017; 39(5):930-45. [DOI:10.1016/j.clinthera.2017.04.004]
[PMID]
[25] Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune
function. Nutrients. 2013; 5(7):2502-21. [DOI:10.3390/
nu5072502] [PMID]
[26] Aranow C. Vitamin D and the immune system. J Investig
Med. 2011; 59(6):881-6. [DOI:10.2310/JIM.0b013e31821b8755]
[PMID]
[27] Lang PO, Samaras N, Samaras D, Aspinall R. How important
is vitamin D in preventing infections? Osteoporos Int.
2013; 24(5):1537-53. [DOI:10.1007/s00198-012-2204-6] [PMID]
[28] van der Starre WE, van Nieuwkoop C, Thomson U, Zijderveld-
Voshart MS, Koopman JP, van der Reijden TJ, et al. Urinary
proteins, vitamin D and genetic polymorphisms as risk
factors for febrile urinary tract infection and relation with bacteremia:
A case control study. PLoS One. 2015; 10(3):e0121302.
[DOI:10.1371/journal.pone.0121302] [PMID]
[29] Hertting O, Holm Å, Lüthje P, Brauner H, Dyrdak R, Jonasson
AF, et al. Vitamin D induction of the human antimicrobial
peptide cathelicidin in the urinary bladder. Plos One. 2010;
5(12):e15580. [DOI:10.1371/journal.pone.0015580] [PMID]
[30] Yang X, Ru J, Li Z, Jiang X, Fan C. Lower vitamin D levels
and VDR FokI variants are associated with susceptibility to
sepsis: A hospital-based case-control study. Biomarkers. 2022;
27(2):188-95. [DOI:10.1080/1354750X.2021.2024598] [PMID]
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