اِرتباط تعدد الاشكال الجيني للانترلوكين 4 (-590 C/T) وعلاقتة بالفشل الكلوي وعدوى المسالك البولية البكتيرية

Rp_ Association of the IL-4 gene polymorphisms(-590 CT) and its relation with renal failuer and bacterial urinary tract infections. pdf

The current study was included the collection of (180) clinical samples of blood and urine samples from three groups of patients, as well as a control group. who were diagnosed clinically by specialized doctors. The first group included patients with renal failure, whose ages ranged from 17-85 years, while the second group included patients with urinary tract infections, whose ages ranged from 18 to 82 years. The third group consisted of patients with urinary tract infection and renal failure at the same time, whose ages ranged between 17-85 years, and 45 patients per group, of both sexes, who attended Imam Hussein (Peace be upon him) Medical City Hospital in the Holy Karbala Governorate and Al-Diwaniyah Teaching Hospital in Diwaniyah Governorate during the period from March to July 2021.
The blood and urine samples were collected from each participant, where the blood sample was divided into two parts, the first part was collected in EDTA tubes to extract DNA, which was used to detect the polymorphism in the IL-4-590 C>T (rs2243250) gene using (Allele-specific PCR) technology. the second part of blood was collected in Gel tubes which used to obtain the serum for the purpose of conducting the ELISA test to determine the level of interleukin 4 (IL-4) in the studied groups. The urine sample was used in the general urine examination and bacterial laboratory culture to isolate and diagnose bacteria in the studied groups.
The results of the demographic analysis showed that there were no significant differences between the tested groups in the mean age repetitively (p = 0.912) and gender (p= 0.145) compared to the control group. It also showed non-significant variations (p= 0.516) in the incidence rate of study groups and place of residence (rural or city), in addition to the lack of association between urinary tract infections and kidney failure with smoking (p = 0.546), while significant differences were found between both urinary tract infections and Renal failure in one herd and both the frequency of infection (p = 0.001), the family history of the patient (p = 0.001) and the presence of kidney stones (p = 0.001). in other had or UTI & renal failer.
The results of bacterial culture showed that out of a total of 135 cultured urine samples, 90 bacterial isolates were obtained, distributed among 45 bacterial isolates from patients with UTI , which were 33 (73.3%) of Gram-negative bacteria, where E. coli 24 occupied (53.3) the which was represented highest percentage of isolates was followed by Acinetobacter baumannii 4 (8.9%), Proteus mirabilis 3 (6.7%) and Pseudomonas aeruginosa 2 (4.4%), while Gram-positive bacteria reached 12 (26.7%), represented by Enterococcus faecalis 4(8.9%), Streptococcus spp. 3(6.7%), Staphylococcus spp. 3 (6.7%), Staphylococcus aureus 2(4.4%).
As for the group of patients with UTI and Renal failure, the number of bacterial isolates was 45, distributed among (77.8%) 35 Gram-negative bacteria isolates (E. coli 27 (60.0%), Acinetobacter baumannii 4.4%) (2), Proteus mirabilis 4 (8.9%) , Pseudomonas aeruginosa 1 (2.2%) , Klebsiella pneumonia 1 (2.2%) and 10 (22.2%) isolates from Gram-positive bacteria represented by Staphylococcus aureus 3 (6.7%), Staphylococcus spp. 1 (2.2%), Streptococcus spp. (8.9% 4) , Enterococcus faecalis 4.4% (2).
The results of the ELISA test showed that there were a significant differences (p ≤ 0.001) in the average level of interleukin 4 in the serum of the study groups. Where the highest rates were recorded in the group of patients with renal failure only, where the average was (295.81 ± 59.73) IU/ml compared to the control group (64.97 ± 36.06) IU/ml.
The results of genetic heterogeneity analysis in the interleukin-4 gene at a locus (rs2243250) by Allele-specific PCR technique showed the agreement of the distribution of the mutations in the study groups according to the (Hardy Weinberg equation). Where the frequency of genotypes CC, TT, and T/C in patients with renal failure was (4, 26, 15), respectively. In addition while was (16,27,2) in patients with UTI , while it reached (4, 34, 7) in the group of patients with UTI and renal failure together compared to the control group, which scored (34, 10, 1) for the studied genotypes, respectively.
The study showed a significant differences in the distribution of genotypes (p < 0.001) and alleles (p < 0.001) for interleukin 4 among study groups compared to the control group. the C/T phenotype was dominant in the all tested groups compared to the control group, in which the CC (75.6%) phenotype was the most prevalent and the C allele (86.7%) was dominant compared to the T allele (13.3%), while the T allele was dominant in the T allele group. In Renal failure patients (62.2%) and patients with renal failure and urinary tract together (53.3%), while whereas the C allele was the most prevalent in the group of patients with urinary tract infection only (65.6%).
When study the association of the interleukin 4 gene polymorphism with different risk factors was investigated, the results did not show a significant correlation (p>0.05) between the interleukin 4 gene polymorphism with all tested factors in the group of patients with renal failure only. on the other had the group of patients with renal failure and urinary tract infection together, which showed significant heterogeneity (p ≤ 0.01) with polymorphism in smoking factor only (p = 0.001) comparison with control groups.
further are the group of patients with UTI only showed significant heterogeneity (p ≤ 0.01) in the genetic polymorphism with both smoking (P= 0.004) and family history (P= 0.001), while the heterogeneity was significant with each of the frequency infections (P= 0.020) and the presence of kidney stones (P= 0.029). The results also clearly show. that there are no significant differences in the mean serum with the different genotypes of interleukin 4 at the probability level (p > 0.05).
The current study concluded that the Gram-negative bacterial species in the study groups were the most common than from Gram-positive bacterial species in the study groups. The CT, TT, and T allele genotypes were also associated with renal failure only and only and renal failure associated with UTI. In addatin only the CT genotype and the T allele were associated with an increased risk of UTI. there was no relationship the serum level of IL-4 between the different genotypes in the different tested groups.