title: Association of IL-6, IL-10, and TNF-α gene polymorphism with malnutrition inflammation syndrome and survival among end stage renal disease patients.
abstract: During end stage renal disease (ESRD) inflammatory pathways are activated which may lead to malnutrition inflammation syndrome (MIS). In the present study, 257 ESRD patients and 200 controls were included. Cytokine levels and genotyping was done by polymerase chain reaction-restriction fragment length polymorphism and enzyme-linked immunosorbent assay (ELISA). Risk was estimated through binary logistic regression. Cox proportional hazards regression and Kaplan-Meier were used for survival analysis. Tumor necrosis factor TNF-α-308 AA conferred 3.6-fold higher susceptibility (P=0.001) and higher TNF-α levels (P=0.05). TNF-α-238 AA was associated with 3.3-fold higher susceptibility to ESRD (P=0.002). IL-6-174 CC genotype conferred 3-fold risk to disease (P=0.001) along with higher IL-6 levels (P=0.001). IL-10-1082 GG genotype exhibited 2.2-fold higher susceptibility to disease (P=0.013). IL-10-592 AA/-819 TT genotypes were associated with high C reactive protein (P=0.02) and low IL-10 (P=0.03) levels. TNF-α-308 A allele was significantly associated with 2.3-fold higher risk of malnutrition. TNF-α-GAC, AGC and IL-6-CC were risk haplotypes associated with higher disease susceptibility. Combined analysis revealed 1.6-fold higher susceptibility to disease (P=0.02), there was 2-fold higher susceptibility to malnutrition (P=0.02) in high inflammation group. TNF-α-238 AA genotype was associated with 2.5-fold higher death hazard risk (P=0.02). Our study suggests that TNF-α and its genetic variants are major contributors to susceptibility to MIS in ESRD patients.
authors.affiliation: Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Sharma
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
authors.forename: Anita
authors.initials: A
authors.lastname: Saxena
authors.forename: R K
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008297:Male; D044342:Malnutrition / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D016019:Survival Analysis; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10