Interleukin 6 (rs1800795) and pentraxin 3 (rs2305619) polymorphisms-association with inflammation and all-cause mortality in end-stage-renal disease patients on dialysis

Abstract

Chronic inflammation plays an important role in the progression and outcome of chronic kidney disease (CKD). The circulating levels of the inflammatory biomarkers interleukin 6 (IL6) and pentraxin 3 (PTX3) are enhanced in CKD patients, and are associated with the progression of the disease and with higher risk for cardiovascular events, the major cause of death in CKD patients. Our aim was to study how specific polymorphisms of IL6 and PTX3 encoding genes affect the inflammatory response and outcome of end-stage renal disease (ESRD) patients on dialysis. Methodology included the analysis of two single nucleotide polymorphisms (SNP), namely the IL6 (rs1800795) polymorphism in the promoter region (-174G > C), and the PTX3 (rs2305619) polymorphism in the intron 1 (+ 281A > G), which were analyzed in ESRD patients on dialysis and in a group of heathy individuals. The allelic frequencies, genotype distribution and their association with circulating levels of the inflammatory markers C-reactive protein (CRP), IL6, growth differentiation factor 15 (GDF15) and PTX3, were determined in ESRD patients. Events of death were recorded along one year, to assess the association of the studied SNPs with all-cause mortality and the inflammatory biomarkers, in ESRD patients. Results showed that the allelic frequencies and genotype distribution for IL6 and PTX3 SNPs in the control group and ESRD patients were similar and in agreement with other European reports. For the IL6 polymorphism, we found a trend towards higher levels of high-sensitivity (hs) CRP, IL6 and PTX3 in the homozygous genotypes; the CC genotype also showed the highest levels of GDF15. The mortality rate after the 1-year follow-up was 10.4%. The CC genotype (IL6 SNP) was associated to a higher risk of mortality and deceased patients carrying this genotype also showed the highest levels of hsCRP. Regarding the studied PTX3 SNP, the AA genotype was linked to an enhanced inflammatory response, showing the highest values of hsCRP and IL6. Nevertheless, this genotype had no significant impact on the mortality rate. In conclusion, both studied SNPs seem to modulate the inflammatory response in ESRD and may, therefore, be determinant on disease progression and patients’ outcome. Our data also highlights the importance of research on genetic variants that, although less frequent, may have significant biological value.

Inflammation and Cardiovascular Disease Associated With Hemodialysis for End-Stage Renal Disease

“…Oxidative stress (OS), which refers to an imbalance between the two antagonistic systems of oxidation and antioxidation in the body, tends to oxidize, causing abnormalities in the biochemical and physiological processes of the body and damage to endothelial tissues ( Formanowicz et al, 2015 ; Kalantar-Zadeh et al, 2016 ; Kalantar-Zadeh et al, 2017 ; Ko et al, 2017 ; Brown-Tortorici et al, 2020 ; Rocha et al, 2021 ; Valga et al, 2021 ). Oxidants of oxidative stress refer to reactive oxygen or nitrogen species (ROS or RNS, respectively) as well as free radicals.…”

Yishen Qingli Heluo Granule Ameliorates Renal Dysfunction in 5/6 Nephrectomized Rats by Targeting Gut Microbiota and Intestinal Barrier Integrity

“…Our previous study found that the key active compound quercetin in YQHG possessed a perfect binding conformation with IL-6 ( Supplementary Figure S2 ). Moreover, researches have found that the expression of IL-6 is closely related to renal inflammation and fibrosis ( Feigerlová and Battaglia-Hsu, 2017 ; Rops et al, 2018 ; Rocha et al, 2021 ). Thus, in this study, IL-6 was selected by us as a potential marker to evaluate renal inflammation.…”

MIF rs755622 and IL6 rs1800795 Are Implied in Genetic Susceptibility to End-Stage Renal Disease (ESRD)

“…On the other hand, in chronic kidney diseases (CKD), MIF limits the pro-fibrotic and proinflammatory activation of tubular cells by counteracting the arrest of the cell cycle and promoting its regeneration; In addition, in acute kidney damage (AKI), MIF also counteracts the apoptosis of tubular cells with a protective effect [ 43 , 82 , 83 ]. So it is possible that the net effect of the presence of rs755622 on CKD predisposition and ESRD progression might be influenced by individual biological factors such as aging [ 84 ] or the presence of comorbidities.…”

“…Key proinflammatory cytokines have been analyzed by different research groups both as circulating markers and as components of the genetic background predisposing to CKD. Cytokines of the TNF family [ 35 , 36 , 37 ], TNF SNPs [ 38 , 39 ], IL-6 serum levels [ 40 , 41 ], and IL6 gene SNPs [ 42 , 43 , 44 ], as well as macrophage inhibiting factor (MIF) and MIF gene variants [ 45 , 46 , 47 , 48 ], might play a role in favoring kidney damage and have been studied. In particular, the rs1800629 and rs1800795 polymorphisms of TNFA and IL6 genes can selectively affect spontaneous production of inflammatory cytokines influencing kidney function decrease and consequent development and progression of chronic kidney disease.…”