Abstract
Chronic inflammation plays an important role in the progression and outcome of chronic kidney disease (CKD). The inflammatory biomarkers interleukin-6 (IL6) and pentraxin 3 (PTX3) are enhanced in CKD patients and associated with progression of the disease and higher risk for cardiovascular events, the major cause of death in these patients. Our aim was to study how the polymorphisms of their encoding genes affect the inflammatory response and outcome of end-stage renal disease (ESRD) patients on dialysis. We analyzed two single nucleotide polymorphisms (SNP), the IL6 (rs1800795) polymorphism in the promoter region (-174G/C), and the PTX3 polymorphism in the intron 1 (+ 281A/G), in ESRD patients on dialysis and in heathy individuals. The allelic frequencies, genotype distribution and their association with the circulating levels of the inflammatory markers high sensitivity C-reactive protein (hsCRP), interleukin (IL6), growth differentiation factor 15 (GDF15) and PTX3, were determined in ESRD patients; events of death were recorded along one year to evaluate all-cause mortality and the association between inflammation and the studied polymorphisms. The allelic frequencies and genotyping distribution for IL6 and PTX3 in controls and ESRD patients were similar and in agreement with European reports. For the IL6 polymorphism, we found an association of the GG and CC genotype with higher IL6 levels; the CC genotype showed also high PTX3, hsCRP and GDF15 levels. For the PTX3 polymorphism, the AA genotype was linked to the highest values of hsCRP and IL6. The mortality rate after 1-year follow-up was 10.4%. The CC genotype (IL6 polymorphism), in deceased patients, was associated to increased levels of hsCRP, IL6 and PTX3, with low levels of GDF15 and with a highest mortality risk. The AA genotype for PTX3 polymorphism, in spite of the enhancement in inflammation, showed no significant impact on mortality. Our results show that the CC genotype of the IL6 polymorphism was associated with an enhanced inflammatory state and a poorer survival rate. Both IL6 and PTX3 polymorphisms seem to modulate the inflammatory response and, therefore, disease progression and outcome. Our data also highlights the importance of research on genetic variants that, although less frequent, may have significant biological value.
Interleukin 6 (rs1800795) and Pentraxin 3 (rs2305619) Polymorphisms - Association with Inflammation and All-Cause Mortality in End-stage-renal Disease Patients on Dialysis