Original Research ArticleThere is no correlation between the functional polymorphism −460C>T of vascular endothelial growth factor (VEGF) gene promoter and uncomplicated recurrent urinary tract infection among young women
Introduction
Recurrent urinary tract infection (RUTI) is an episode of urinary tract infection (UTI) at least two times in six months or three or more re-infections with clinical symptoms in a year. RUTI is one of the major causes of renal scars; it also increases the incidence of renal insufficiency and hypertension, contributes to high morbidity and increases health care costs. Some studies found that RUTI was related to behavioral risk factors (sexual activities, diaphragm and spermicidal use, antibiotics use or estrogen use),1, 2, 3 host factors for instance a short anatomical distance between the urethra and anus,1, 2 and genetic factors such as polymorphisms in several genes that encode cytokines and inflammatory mediators.4, 5
Vascular endothelial growth factor (VEGF, referred to VEGF-A in this study) is a key mediator of normal and abnormal angiogenesis (proliferation, sprouting, migration and tube formation of endothelial cells) and an important regulator of vascular permeability.6, 7 In addition, several studies found that VEGF is an important molecule in several diseases.7, 8, 9, 10, 11 VEGF belongs to VEGF family that includes VEGF-B, VEGF-C, VEGF-D and placenta growth factor (PlGF).6 Because VEGF has pivotal roles in endothelial cells – an important medium of transporting immune system components between blood circulation and epithelial compartment – therefore, it could has important roles in infection including UTI.
VEGF gene, located on chromosome 6 at 6p21.3, is organized in 8 exons separated by 7 introns and the coding region encompasses approximately 14 kb.12 VEGF gene is highly polymorphic and numerous single nucleotide polymorphisms (SNPs) can be found in the promoter and 5′ untranslated region (5′-UTR).13, 14 Common SNPs in VEGF gene have been studied and one of the most consistent SNP with several diseases is VEGF −460C>T. Study found that the person with VEGF −460C allele had higher VEGF protein expression15 and VEGF −460C>T polymorphism had strong correlation with susceptibility, development, progressivity and prognosis of several diseases.16, 17, 18, 19, 20, 21, 22
Focusing on urinary tract diseases, a previous study revealed that VEGF −460C>T polymorphism is related to renal parenchymal scarring in childhood UTI.23 Another study found that UTI cases (with or without vesicoureteral reflux (VUR) complication) had association with VEGF −460C>T polymorphism.24 However, there was no association of this polymorphism with uncomplicated-UTI.24 Another study also found similar findings.25 They found that VEGF −460 CC genotype was more frequent in UTI with VUR complication cases compared to healthy controls or UTI without VUR complication cases. However, the role of this polymorphism in uncomplicated RUTI is still unknown.
Section snippets
Aim
The objective of this present study was to determine the correlation between VEGF −460C>T polymorphism and uncomplicated RUTI among young women.
Subjects
This case–control study was conducted with 34 culture-confirmed uncomplicated RUTI cases in young women (age range was 15–50 years old) and 34 normal women. Uncomplicated RUTI criteria that were applied in this study have been published previously.26 Uncomplicated RUTI criteria in this study were: (a) UTI that occurred three times or more in 12 months or two times or more in 6 months; (b) no structural and functional abnormality of the urinary tract (based on standard blood urea nitrogen and
Subject characteristics and risk factors
In this study, 34 young women with uncomplicated RUTI (mean age was 32 ± 6.59 years old) and 34 controls (mean age was 26.1 ± 5.2 years old) were enrolled. Among the cases, 11 had three times UTI in a year and 23 cases suffered from UTI three times in six months. There were 27 with lower UTI (cystitis or bladder infection) and 7 with upper UTI (ureters infection); 80% of infection were caused by Escherichia coli.
The list of RUTI risk factors is presented in Table 1. Briefly, age, marital status,
Discussion
There are several risk factors of RUTI such as frequent sexual intercourse, use of contraception (intrauterine device, diaphragm and spermicidal), use of antibiotics, estrogen levels, and anal and urethra anatomy.1, 2, 28, 29 This study results support previous findings that sexual intercourse frequency, marital status and intrauterine device contraception were correlated with RUTI. In this study, the age between case and control groups was not matched properly; therefore, age seems as an
Conclusions
This present study found that there was no association between VEGF −460C>T polymorphism of VEGF gene promoter and uncomplicated RUTI among young women.
Conflict of interest
There is no conflict of interest.
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