Relative risk for cardiovascular morbidity in hemodialysis patients regarding gene polymorphism for IL-10, IL-6, and TNF

Abstract

Uremia-related inflammation is prone to be a key factor to explain high cardiovascular morbidity in hemodialysis patients. Genetic susceptibility may be of importance, including IL-10, IL-6, and TNF. The aim was to analyze IL-10, IL-6, and TNF gene polymorphisms in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity. This study included 169 patients on regular hemodialysis at Zvezdara University Medical Center. Gene polymorphisms for IL-10, IL-6 and TNF were determined using PCR. These findings were correlated with the cardiovascular morbidity data from patient histories. Heterozygots for IL-10 gene showed significantly lower incidence of cardiovascular events (p = 0.05) and twice lower risk for development of myocardial infarction, but experienced twice higher risk for left ventricular hypertrophy. Regarding TNF gene polymorphism, patients with A allele had 1.5-fold higher risk for cerebrovascular accident and cardiovascular events and 2-fold higher risk for hypertension and peripheral vascular disease. Patients with G allele of IL-6 gene experienced 1.5-fold higher risks for cerebrovascular accident. We need studies with larger number of patients for definitive conclusion about the influence of gene polymorphisms on cardiovascular morbidity in hemodialysis patients and its importance in everyday clinical practice.

Cytokines Genotype‐Phenotype Correlation in Nonalcoholic Steatohepatitis

“…In our study, the CC genotype was correlated with associated hypertension, while in the study by Tosic-Dragovic et al [ 32 ] patients with G allele of the IL-6 gene experienced 1.5-fold higher risks for cerebrovascular accident. A meta-analysis [ 33 ] revealed that IL-6 -174 G/C polymorphism was not significantly associated with hypertension under all of the genetic models, but the authors concluded that several studies are needed especially in Europeans and Middle-Eastern populations.…”

Polymorphism related to cardiovascular risk in hemodialysis subjects: a systematic review

“…Different haplotypes in the IL-6 gene can determine the levels of its transcription. The IL-6 gene is located on chromosome 7p21 and has several polymorphisms in the promoter regions (-174 G/C, -634 C/G, -572 G/C and -597 G/A)17 associated with increased risk of CVD.…”

“…In this context, Song et al8 published that genotypes IL-6-634GG and IL-6-174CC were associated with a higher risk of cardiovascular events in HD individuals. Nonetheless, Tosic Dragovic et al,17 in addition to IL-6, also evaluated polymorphisms in IL-10 and TNF and concluded that cardiovascular morbidity could be under the influence of genetic polymorphisms in these cytokines.…”

Opportunities and Challenges for Genetic Studies of End-Stage Renal Disease in Canada

“…Evidence is limited to candidate gene association studies, which have significant issues with reproducibility and publication bias. Studies looked for SNP associations with hemodialysis outcomes including vascular access issues, 56 - 61 biochemical indices, 62 - 65 inflammation, 66 - 68 cardiovascular comorbidities 66 , 69 - 75 and mortality 76 - 79 and PD outcomes including peritoneal transport characteristics, 80 - 84 peritonitis risk, 85 - 87 or risk of encapsulating peritoneal sclerosis 88 ( Supplemental Table 1 ). Sample sizes were inadequate to confidently identify variants of reasonable effect sizes (average sample size of 246, range 67-777 patients).…”