Kamini Singh1,2, Kashi Nath Prasad3, Priyanka Mishra1, Jahanarah Khatoon1, Narayan Prasad4, Amit Gupta4, Janmejai Kumar Srivastava2. 1. Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India. 2. Amity Institute of Biotechnology, Amity University, Uttar Pradesh, Lucknow, India. 3. Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India. kashinprasad@gmail.com. 4. Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Abstract
BACKGROUND: Toll-like receptors (TLRs), expressed on cells of the innate immune system, are the first line of host defense. Recognition of bacterial pathogens by the peritoneum is mediated in part by TLR. In this study, we investigated the role of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg677Trp and Arg753Gln) gene polymorphisms in end-stage renal disease (ESRD) patients on peritoneal dialysis (PD). METHOD: A total of 100 ESRD patients on PD and 150 healthy controls were enrolled in the study. The patients were divided into two groups: ESRD patients on PD with peritonitis (n = 38) and without peritonitis (n = 62). Genotyping of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg677Trp and Arg753Gln) genes were performed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). RESULTS: Heterozygous variant of TLR4 (Thr399Ile) Thr/Ile genotype showed significant association with both groups of patients (patients with and without peritonitis) with no difference between the groups. Overall, TLR4 (Thr399Ile) Thr/Ile genotype demonstrated an association with ESRD on PD (OR 3.9). Further, TLR4 (Thr399Ile) polymorphism showed significant association with PD patients having two or more episodes of peritonitis compared to patients with no peritonitis. No such association of increased risk of ESRD was observed with TLR4 (Asp299Gly) Asp/Gly genotype and TLR2 polymorphisms. Haplotype frequencies, Gly/Ile and Asp/Ile, conferred 2.46- and 4.62-fold increased risk of ESRD, respectively. CONCLUSIONS: TLR4 Thr399Ile genotype was associated with ESRD patients on PD; however, the genotype frequency was similar in PD patients with and without peritonitis.
BACKGROUND: Toll-like receptors (TLRs), expressed on cells of the innate immune system, are the first line of host defense. Recognition of bacterial pathogens by the peritoneum is mediated in part by TLR. In this study, we investigated the role of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg677Trp and Arg753Gln) gene polymorphisms in end-stage renal disease (ESRD) patients on peritoneal dialysis (PD). METHOD: A total of 100 ESRDpatients on PD and 150 healthy controls were enrolled in the study. The patients were divided into two groups: ESRDpatients on PD with peritonitis (n = 38) and without peritonitis (n = 62). Genotyping of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg677Trp and Arg753Gln) genes were performed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). RESULTS: Heterozygous variant of TLR4 (Thr399Ile) Thr/Ile genotype showed significant association with both groups of patients (patients with and without peritonitis) with no difference between the groups. Overall, TLR4 (Thr399Ile) Thr/Ile genotype demonstrated an association with ESRD on PD (OR 3.9). Further, TLR4 (Thr399Ile) polymorphism showed significant association with PDpatients having two or more episodes of peritonitis compared to patients with no peritonitis. No such association of increased risk of ESRD was observed with TLR4 (Asp299Gly) Asp/Gly genotype and TLR2 polymorphisms. Haplotype frequencies, Gly/Ile and Asp/Ile, conferred 2.46- and 4.62-fold increased risk of ESRD, respectively. CONCLUSIONS:TLR4 Thr399Ile genotype was associated with ESRDpatients on PD; however, the genotype frequency was similar in PDpatients with and without peritonitis.
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