Association of IL-10 genotypes with cardiovascular risk factors in patients with hemodialysis

Ko, Gang Jee; Kim, Jeong Yup; Kim, Myung Kyu; Suh, Soon Yong; Choi, Hye Min; Hyun, Young Youl; Boo, Chang Su; Lee, Jee Eun; Sung, Su Ah; Jo, Sang Kyung; Cho, Won Yong; Kim, Hyeong Gyu

Abstract

BACKGROUND: Chronic systemic inflammation in ESRD patients due to uremia and hemodialysis procedure itself comes into notice as a main factor for premature mortality secondary to rapid progressing atherosclerosis. Various pro-inflammatory cytokine, known to mediate these reaction of malnutrition, inflammation and atherosclerosis, are regulated by anti-inflammatory cytokine, such as IL-10. Quantitative production of IL-10 shows interindividual variability determined genetically by polymorphisms of promotor gene. The aim of this study was to measure the degree of IL-10 synthesis in ESRD patients treated with hemodialysis and evaluate the association with genotypes and cardiovascular risk factors.
METHODS
The IL-10 genotypes for polymorphic bases at position at -1082 was determined in 66 chronic hemodialysis patients and 98 healthy subjects using highly specific PCR and the lipopolysaccharide (LPS)-stimulated IL-10 (sIL-10) release from whole blood were measured by ELISA.
RESULTS
The distribution of the IL-10 genotypes in hemodialysis patients were similar to the general population, but the proportion of A allele in hemodialysis group was significantly higher (72.3% vs 59.8%, p=0.05). sIL-10 concentration were lower in hemodialysis patients compared with normal control (21.1 pg/mg vs 36.1 pg/mg, p=0.001) and both groups showed same relationship of sIL-10 with genotypes, that AA type was low producer. In multiple regression analysis, sIL-10 of normal group correlated negatively with age, creatinine, uric acid and existence LVH, and positively with albumin, hemoglobin. On the other hand, lower albumin, lower ejection fraction on echocardiography and existence of left ventricular hypertrophy were associated with higher sIL-10 in hemodialysis group.
CONCLUSION
Polymorphisms by IL-10 genotypes were associated with production of IL-10 by endotoxin stimulation, and sIL-10 was lower in hemodialysis patients than in normal control. According to relation of sIL-10 with cardiovascular risk factors such as existence LVH, ejection fraction and malnutrition, it could be suggested that sIL-10 is useful marker in evaluating the risk of cardiovascular events.