Gene polymorphism association studies in dialysis: the nutrition-inflammation axis

Although traditional risk factors for cardiovascular disease are common in dialysis patients, they alone cannot explain the unacceptably high prevalence of vascular disease in this patient group. Much recent interest has therefore focused on the role of various nontraditional cardiovascular risk factors, such as inflammation, wasting, obesity, vascular calcification, and oxidative stress. In addition, genetic factors such as single nucleotide polymorphisms (SNPs) may significantly influence the immune response, the levels of inflammatory markers and body composition, as well as the prevalence of vascular calcification in this patient group. While genetic variations in the tumor necrosis factor (TNF)-alpha-308 and interleukin (IL)-10 -1082 SNPs seem to be consistently associated with adverse clinical outcome in end-stage renal disease (ESRD) patients, the results regarding genetic variations in the IL-6 gene have been conflicting. To elucidate the respective role of DNA polymorphisms in the IL-6 and C-reactive protein (CRP) genes, as well as genes that encode vascular calcification inhibitors (such as fetuin-A, matrix Gla protein, and osteoprotegerin), sufficiently powered studies are needed in which both the protein product and the specific phenotype are determined. In addition, polymorphisms in genes related to body composition may be excellent candidates for analysis in the ESRD population, since nutritional parameters are strongly associated with adverse events in these patients. It seems conceivable that in the future, prognostic or predictive multigene DNA assays (which allow a simultaneous and rapid assessment of multiple genetic variants) will provide nephrologists with a more precise approach for the identification of "high-risk" ESRD patients and the development of accurate individualized treatment strategies.