Cytokine gene polymorphism and progression of renal and cardiovascular diseases.
Cytokines are important modulators of inflammation. The balance between pro- and anti-inflammatory cytokines determines whether the intensity of inflammatory response is within physiological limits or in the pathological range. The cytokine network is highly complex, containing interactive cascades of gene activation and suppression. Both chronic kidney disease (CKD) and end-stage renal disease (ESRD) are characterized by elevated levels of proinflammatory cytokines and markers of inflammation. Cytokines may modulate the risk for progression of renal disease and the susceptibility to cardiovascular disease (CVD). Polymorphisms of cytokine genes may influence gene transcription and cytokine secretion and thereby modulate the risk of progression of renal and CVDs. The observed inconsistencies in the data regarding associations between single-nucleotide gene polymorphisms (SNPs) and their presumed phenotypic expression emphasize the need to recognize several conceptual and methodological aspects such as haplotypic rather than single SNP variations and the influence of pathway genes with synergistic or antagonistic effects that ultimately determine the phenotype. It is conceivable that when a patient with a high-risk cytokine genotype develops CKD, the risk for CVD is increased. Early interventions in CKD patients with high-risk genotypes may slow the progression of renal disease and also decrease CV mortality and morbidity.
Rao
M
M
Division of Nephrology, Tufts-New England Medical Center, Boston, Massachusetts, USA.
Wong
C
C
Kanetsky
P
P
Girndt
M
M
Stenvinkel
P
P
Reilly
M
M
Raj
D S C
DS
D002318:Cardiovascular Diseases / Q000209:etiology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics*; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000209:etiology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D011110:Polymorphism, Genetic
D016207:Cytokines