RESUMEN
End-stage renal disease (ESRD) is a serious health problem worldwide. The high prevalence of cardiovascular diseases and chronic inflammation remains a major cause of morbidity and mortality in haemodialysed patients. Beside some external factors, genetic predisposition both to renal failure and poor prognosis has been assumed. We have collected a total of 1,014 haemodialysed patients and 2,559 unrelated healthy Caucasians. Single-nucleotide polymorphisms (SNPs) in genes for preproghrelin (GHRL), lipopolysaccharide-binding protein (LBP), HFE and MTHFR were genotyped. In the group of patients, significantly more carriers presented the MTHFR T667T (P = 0.002) and HFE Asp63Asp (P = 0.001) and Cys282Cys (P = 0.01) genotypes. The frequencies of individual SNPs within GHRL and LBP genes did not differ between the patients and controls. The trends in genotype frequencies did not differ between the subgroups of patients with different time on haemodialysis. Common variants in MTHFR and HFE could be a risk factor for all-cause ESRD development, but are not predictors for the survival on haemodialysis.
Asunto(s)
Proteínas de Fase Aguda/genética , Proteínas Portadoras/genética , Ghrelina/genética , Antígenos de Histocompatibilidad Clase I/genética , Fallo Renal Crónico/genética , Glicoproteínas de Membrana/genética , Proteínas de la Membrana/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad/genética , Proteína de la Hemocromatosis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The dysbalance in the expression of proinflammatory and anti-inflammatory cytokines, which is partially genetically determined, might have essential impact on the clinical outcome and survival of haemodialysed (HD) patients. A total of 500 HD patients and 500 healthy controls were genotyped for three single-nucleotide polymorphisms (SNPs: TNFA -308G/A, IL10 -1082G/A, IFNG +874A/T). To detect the SNPs' impact on clinical outcome and survival, the HD population was divided into two subgroups depending on the length of HD therapy. The genotypes and phenotypes were correlated with two years followed up laboratory parameters and survival of HD patients. The one-year HD departed patients exhibited significantly higher age (P = 0.0167), C-reactive protein (P = 0.0012), lower nutritional (body mass index, P = 0.0168; dry weight, P = 0.0207; albumin, P = 0.005; triglycerides, P = 0.0174), haematological (red blood cells count, P = 0.0210; haemoglobin, P = 0.0159; haematocrit, P = 0.0368) and HD efficacy parameters (Kt/V, P = 0.0273) compared to long-term HD survivors. Both HD and control population showed similar genotype distribution except for higher occurrence of TNFA A/A homozygotes in healthy controls (P = 0.008). There were no differences in both genotypes and phenotypes in HD subgroups because of the low number of patients in one- -year HD departed patients. Neither genotype nor phenotype had an impact on patients' survival. From our results we cannot infer that the promoter region SNPs of immune system response-regulating cytokines IL-10, TNF-α and IFN-γ have a major impact on clinical outcome of patients on maintenance haemodialysis.
Asunto(s)
Interferón gamma/genética , Interleucina-10/genética , Fallo Renal Crónico/genética , Fallo Renal Crónico/terapia , Polimorfismo de Nucleótido Simple , Diálisis Renal , Factor de Necrosis Tumoral alfa/genética , Anciano , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Femenino , Genotipo , Humanos , Fallo Renal Crónico/epidemiología , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Heritability studies have estimated the genetically attributable part of body mass index variance to be in the range of 30-70 %. Rs7566650 (G>C) single-nucleotide polymorphism (SNP) near the promoter of the INSIG2 gene has been identified as associated with body mass index. The gene product of INSIG2 is involved in regulation of fatty acid and cholesterol synthesis. In order to replicate this association we have analysed 2,559 unrelated individuals of Slavonic Caucasian origin from the populationbased Czech MONICA 3-year cohort. Body mass index, waist-hip ratio and plasma lipids (total-cholesterol, HDL-cholesterol, triglycerides) were measured at two independent examinations within three years. We could not detect any association between the SNP rs7566605 and body mass index, waist-hip ratio or lipid parameters, both with or without adjusting for age and gender. Neither the body mass index change nor lipid changes were significantly affected by the INSIG2 gene variant. Our results indicated that this INSIG2 polymorphism has no significant effect on body mass index and plasma lipids in the Czech Slavonic population.