Abstract
It is known that small alterations leading to different vitamin D receptor (VDR) alleles affect resistance or susceptibility to infections. In this study, we examined VDR gene polymorphisms in urinary tract infections (UTI), which are common and an important cause of morbidity in children and subsequently of renal scar formation. We evaluated 92 patients diagnosed with UTI and 105 children without prior history of UTI as a control group. The VDR gene polymorphisms BsmI, FokI, ApaI, and TaqI were evaluated in patients and controls. BsmI polymorphism genotype distribution was similar between groups. There was a significant difference between groups for FokI (p = 0 < 001); for the ff genotype, the risk of UTI was significantly increased (p < 0.01) ,at 3.94 times higher (odds ratio = 3.94; 95% confidence interval 1.71-9.09). ApaI polymorphism was significantly increased in the control group (p < 0.01) and evaluated as a protective factor. Comparing the TaqI genotype between groups, there was no statistically significant difference, but in both Tt and tt genotypes, there was minimal increased risk of UTI. The results of this study suggest that VDR gene polymorphisms can be important for susceptibility to UTI and renal scar formation. Association between VDR polymorphisms and UTI is in accordance with the understanding of how vitamin D modulates the immune response against infections.
Similar content being viewed by others
References
Craig JC (2001) Urinary tract infection: new prospectives on a common disease. Curr Opin Infect Dis 14:309–313
Jahnukainen T, Chen M, Celsi G (2005) Mechanisms of renal damage owing to infection. Pediatr Nephrol 20:1043–1053
Haraoka M, Hang L, Frendeus B, Godaly G, Burdick M, Strieter R, Svanborg C (1999) Neutrophil recruitment and resistance to urinary tract infections. J Infect Dis 180:1220–1229
Cotton SA, Gbadegesin RA, Williams S, Brenchley PEC, Webb NJA (2002) Role of TGF-β in renal parenchymal scarring following childhood urinary tract infection. Kidney Int 61:61–67
Artifoni L, Negrisolo S, Montini G, Zucchetta P, Molinari PP, Cassar W, Destro R, Anglani F, Rigamonti W, Zacchello G, Murer L (2007) Interleukin-8 and CXCR1 receptor functional polymorphisms and susceptibility to acute pyelonephritis. J Urol 177:1102–1106
Dusso AS, Brown AJ, Slatopolsky E (2005) Vitamin D. Am J Physiol Renal Physiol 289:F8–F28
Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338:143–156
Leandro ACSS, Rocha MA, Cardoso CSA, Bonecini-Almeida MG (2009) Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-γ genes and its association with susceptibility to tuberculosis. Braz J Med Biol Res 42:312–322
White JH (2008) Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun 76:3837–3843
Lewis SJ, Baker I, Smith GD (2005) Meta-analysis of vitamin D receptor polymorphisms and pulmonary tuberculosis risk. Int J Tuberc Lung Dis 9:1174–1177
Dusso AS, Negrea L, Gunawardhana S, Lopez-Hilker S, Finch J, Mori T, Nishii Y, Slatopolsky E, Brown AJ (1991) On the mechanisms for the selective action of vitamin D analogs. Endocrinology 128:1687–1692
Gibney KB, MacGregor L, Leder K, Torresi J, Marshall C, Ebeling PR, Biggs BA (2008) Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. Clin Infect Dis 46:443–446
Kawarau A, Takeda E, Tanida N, Nakagawa K, Yamamoto H, Sawada K, Okano T (2006) Inhibitory effect of long term 1-alpha-hydroxyvitamin D3 administration on Helicobacter pylori infection. J Clin Biochem Nutr 38:103–106
Brook I (2005) Microbiology and antimicrobial management of sinusitis. J Laryngol Otol 119:251–258
Montone KT (2007) Infectious diseases of the head and neck: a review. Am J Clin Pathol 128:35–67
Wolf J, Daley AJ (2007) Microbiological aspects of bacterial lower respiratory tract illness in children: atypical pathogens. Paediatr Respir Rev 8:212–220
Wayse V, Yousafzai A, Mogale K, Filteau S (2004) Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr 58:563–567
Muhe L, Lulseged S, Mason KE, Simoes EAF (1997) Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children. Lancet 349:1801–1804
Laaksi I, Ruohola J-P, Tuohimaa P, Auvinen A, Haataja R, Pihlajamaki H, Ylikomi T (2007) An association of serum vitamin D concentrations <40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr 86:714–717
Poon AH, Laprice C, Lemire M, Montpetit A, Sinnett D, Schurr E, Hudson TJ (2004) Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy. Am J Respir Crit Care Med 170:967–973
Roth DE, Soto G, Arenas F, Bautista CT, Ortiz J, Rodriguez R, Cabrera L, Gilman RH (2004) Association between vitamin D receptor gene polymorphisms and response to treatment of pulmonary tuberculosis. J Infect Dis 190:920–927
Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, Wright D, Latif M, Davidson RN (2000) Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet 355:618–621
Roth DE, Jones AB, Prosser C, Robinson JL, Vohra S (2008) Vitamin D receptor polymorphisms and the risk of acute lower respiratory tract infection in early childhood. J Infect Dis 197:676–680
Barber Y, Rubio C, Fernández E, Rubio M, Fibla J (2001) Host genetic background at CCR5 chemokine receptor and vitamin D receptor loci and human immunodeficiency virus (HIV) type 1 disease progression among HIV-seropositive injection drug users. J Infect Dis 184:1279–1288
De la Torre MS, Torres C, Nieto G, Vergara S, Carrero AS, Macia J, Pineda JA, Caruz A, Fibla J (2008) Vitamin D receptor gene haplotypes and susceptibility to HIV-1 infection in injection drug users. J Infect Dis 197:405–410
Bellamy R, Ruwende C, Corrah T, Mc Adam KP, Thursz M, Whittle HC, Hill AV (1999) Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene. J Infect Dis 179:721–724
Fitness J, Tosh K, Hill AVS (2002) Genetics of susceptibility to leprosy. Genes Immun 3:441–453
Roy S, Frodsham A, Saha B, Hazra SK, Mascie-Taylor CG, Hill AV (1999) Association of vitamin D receptor genotype with leprosy type. J Infect Dis 179:187–191
Zasloff M (2007) Antimicrobial peptides, innate immunity, and the normally sterile urinary tract. J Am Soc Nephrol 18:2810–2816
Equils O, Naiki Y, Shapiro AM, Michelsen K, Lu D, Adams J, Jordan S (2006) 1,25-Dihydroxyvitamin D3 inhibits lipopolysaccharide-induced immune activation in human endothelial cells. Clin Exp Immunol 143:58–64
Gombart AF, Borregaard N, Koeffler HP (2005) Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J 19:1067–1077
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Aslan, S., Akil, I., Aslan, G. et al. Vitamin D receptor gene polymorphism in children with urinary tract infection. Pediatr Nephrol 27, 417–421 (2012). https://doi.org/10.1007/s00467-011-2000-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-011-2000-0