Toll-like receptors TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg677Trp and Arg753Gln) gene polymorphisms in end-stage renal disease patients on peritoneal dialysis.
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).


METHODS
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.
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.|Amity Institute of Biotechnology, Amity University, Uttar Pradesh, Lucknow, India.
Kamini
K
Singh
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India. kashinprasad@gmail.com.
Kashi Nath
KN
Prasad
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
Priyanka
P
Mishra
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
Jahanarah
J
Khatoon
Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Narayan
N
Prasad
Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Amit
A
Gupta
Amity Institute of Biotechnology, Amity University, Uttar Pradesh, Lucknow, India.
Janmejai Kumar
JK
Srivastava
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects; D010538:Peritonitis / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
ESRD; Peritoneal dialysis; Polymorphism; Toll-like receptor