RESUMO
La nefronoptisis es una enfermedad renal quística, de herencia autosómica recesiva, causada por mutaciones en genes que codifican proteínas involucradas en la función de cilios primarios, lo que resulta en enfermedad renal y manifestaciones extrarrenales como degeneración retiniana y fibrosis hepática. Según la edad de desarrollo de enfermedad renal crónica terminal, se describen tres formas clínicas de presentación: infantil, juvenil y adolescente. El diagnóstico se realiza por una prueba genética positiva o una biopsia de riñón que demuestre cambios tubulointersticiales crónicos con un engrosamiento de las membranas basales tubulares. No existe hasta la actualidad una terapia curativa, por lo que el trasplante renal oportuno es determinante en cuanto al pronóstico. Se presenta un paciente de 13 meses de edad con poliuria de 3 meses de evolución, insuficiencia renal, anemia y elevación de transaminasas. Con hallazgos histológicos compatibles en la biopsia renal, se arribó al diagnóstico de nefronoptisis infantil, con afectación hepática
Nephronophthisis is an autosomal recessive cystic kidney disease caused by mutations in genes that encode proteins involved in the primary cilia function, resulting in kidney disease and extrarenal manifestations such as retinal degeneration and liver fibrosis. According to the age of development of end-stage chronic kidney disease, three clinical forms of presentation are described: infantile, juvenile and adolescent. Diagnosis is made by a positive genetic test, or a kidney biopsy demonstrating chronic tubulointerstitial changes with thickening of the tubular basement membranes. At the moment there is no healing therapy, so early kidney transplant is a fundamental tool to improve prognosis.We present a 13-month old male patient with polyuria, kidney failure, anemia and elevated aminotransferases over three months. With compatible histological kidney biopsy, the diagnosis of infantile nephronophthisis with liver involvement was reached.
Assuntos
Humanos , Masculino , Lactente , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/genética , Doenças Renais Císticas/patologia , Nefropatias , Falência Renal Crônica/genética , Proteínas , Testes GenéticosRESUMO
ABSTRACT Cardiovascular disease (CVD) is one of the leading causes of mortality in hemodialysis (HD) subjects. In addition to the traditional risk factors that are common in these individuals, genetic factors are also involved, with emphasis on single nucleotide polymorphs (SNPs). In this context, the present study aims to systematically review the studies that investigated the polymorphisms associated with cardiovascular risk in this population. In general, the SNPs present in HD individuals are those of genes related to inflammation, oxidative stress and vascular calcification, also able of interfering in the cardiovascular risk of this population. In addition, polymorphisms in genes related to recognized risk factors for CVD, such as dyslipidemia, arterial hypertension and left ventricular hypertrophy, also influence cardiovascular morbidity and mortality.
RESUMO A doença cardiovascular (DCV) é uma das principais causas de mortalidade de indivíduos em hemodiálise (HD). Além dos fatores de risco tradicionais, que são frequentes nesses indivíduos, também estão envolvidos fatores genéticos, com destaque para os polimorfismos de nucleotídeo único (do inglês, single nucleotide polymorphism, SNP). O presente trabalho tem como objetivo revisar sistematicamente os estudos que investigaram os polimorfismos associados ao risco cardiovascular nessa população. De modo geral, os SNPs presentes em indivíduos em HD são aqueles de genes relacionados à inflamação, estresse oxidativo e calcificação vascular, também capazes de interferir no risco cardiovascular dos pacientes. Polimorfismos em genes relacionados a fatores de risco reconhecidos para DCV, como dislipidemia, hipertensão arterial e hipertrofia ventricular esquerda, também influenciam a morbidade e mortalidade cardiovascular.
Assuntos
Humanos , Doenças Cardiovasculares/genética , Diálise Renal , Polimorfismo de Nucleotídeo Único , Falência Renal Crônica/genética , Falência Renal Crônica/terapia , Doenças Cardiovasculares/complicações , Fatores de Risco , Falência Renal Crônica/complicaçõesRESUMO
Background: End-stage kidney disease patients continue to have markedly increased cardiovascular disease morbidity and mortality. Analysis of genetic factors connected with the renin-angiotensin system that influences the survival of the patients with end-stage kidney disease supports the ongoing search for improved outcomes. Objective: To assess survival and its association with the polymorphism of renin-angiotensin system genes: angiotensin I-converting enzyme insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis. Methods: Our study was designed to examine the role of renin-angiotensin system genes. It was an observational study. We analyzed 473 chronic hemodialysis patients in four dialysis units in the state of Rio de Janeiro. Survival rates were calculated by the Kaplan-Meier method and the differences between the curves were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used logistic regression analysis and the multinomial model. A p value ≤ 0.05 was considered to be statistically significant. The local medical ethics committee gave their approval to this study. Results: The mean age of patients was 45.8 years old. The overall survival rate was 48% at 11 years. The major causes of death were cardiovascular diseases (34%) and infections (15%). Logistic regression analysis found statistical significance for the following variables: age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater than five times the minimum wage (p = 0.03089), the latter being a protective factor. Conclusions: The survival of hemodialysis patients is likely to be influenced by the TT of the angiotensinogen M235T gene. .
Fundamento: Os pacientes em hemodiálise continuam tendo um significativo aumento na morbiletalidade, especialmente a causada por doenças cardiovasculares. A análise dos fatores genéticos ligados ao sistema renina-angiotensina que influenciam na sobrevivência destes pacientes poderá ajudar na busca por melhores resultados. Objetivo: Avaliar a sobrevida em hemodialisados e sua associação com polimorfismo dos genes do sistema reninaangiotensina: deleção/inserção do gene que codifica a enzima conversora da angiotensina I e o M235T do angiotensinogênio. Métodos: Estudo observacional desenhado para ver o papel dos genes do sistema renina-angiotensina. Foram analisados 473 pacientes tratados com hemodiálise crônica em quatro unidades de diálise do Estado do Rio de Janeiro. As taxas de sobrevida foram calculadas pelo método de Kaplan-Meier e as diferenças entre as curvas avaliadas pelos testes de: Tarone-Ware, Peto-Prentice e Log-rank. Foram utilizados também modelos de regressão logística e multinomial. Um valor de p ≤ 0,05 foi considerado estatisticamente significativo. O comitê de ética aprovou este estudo. Resultados: A idade média dos pacientes foi de 45,8%. A taxa de sobrevida global foi de 48% em 11 anos. As principais causas de óbito foram: doenças do aparelho circulatório (34 %) e infecções (15%). A análise de regressão logística encontrou significância estatística para as seguintes variáveis: idade, o TT do angiotensinogênio e a renda familiar acima de cinco salários mínimos, esta última como fator de proteção (p valor: 0,000038, 0,08261 e 0,03089, respectivamente). Conclusões: Nossos dados sugerem que o risco de letalidade em pacientes em hemodiálise pode ser influenciado também pelo polimorfismo ...
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angiotensinogênio/genética , Falência Renal Crônica/genética , Falência Renal Crônica/mortalidade , Peptidil Dipeptidase A/genética , Polimorfismo Genético/genética , Diálise Renal/mortalidade , Sistema Renina-Angiotensina/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/mortalidade , Complicações do Diabetes , Estimativa de Kaplan-Meier , Falência Renal Crônica/terapia , Modelos Logísticos , Fatores de Risco , Fatores de TempoRESUMO
Polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T is one of the suggested risk factors for atherosclerosis. However, few studies have reported on the relationship between MTHFR C677T polymorphism and vascular calcification (VC) in chronic hemodialysis patients. We investigated the relationship between the MTHFR C677T polymorphism and VC in 152 chronic hemodialysis patients. Patients with a TT genotype exhibited significantly higher VC scores than patients expressing CC and CT (P = 0.002). The prevalence of peripheral vascular disease increased with the incidence of MTHFR C677T mutations for all patients, and the incidence of cerebrovascular accidents also increased with the presence of mutations for young patients (< or = 60 yr) (P < 0.05). Patients with CT and TT genotypes had adjusted odds ratios for VC of 1.39 and 1.58, respectively (P < 0.05). In summary, these data suggest that the MTHFR C677T polymorphism affects the degree of VC in chronic hemodialysis patients.
Assuntos
Idoso , Humanos , Pessoa de Meia-Idade , Calcinose/genética , Predisposição Genética para Doença , Falência Renal Crônica/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Diálise Renal , Fatores de Risco , Doenças Vasculares/genéticaRESUMO
Nail-patella syndrome (NPS) is an autosomal dominant disease that typically involves the nails, knees, elbows and the presence of iliac horns. In addition, some patients develop glomerulopathy or adult-onset glaucoma. NPS is caused by lossof- function mutations in the LMX1B gene. In this study, phenotype-genotype correlation was analyzed in 9 unrelated Korean children with NPS and their affected family members. The probands included 5 boy and 4 girls who were confirmed to have NPS, as well as 6 of their affected parents. All of the patients (100%) had dysplastic nails, while 13 patients (86.7%) had patellar anomalies, 8 (53.3%) had iliac horns, 6 (40.0%) had elbow contracture, and 4 (26.7%) had nephropathy including one patient who developed end-stage renal disease at age 4.2. The genetic study revealed 8 different LMX1B mutations (5 missense mutations, 1 frame-shifting deletion and 2 abnormal splicing mutations), 6 of which were novel. Genotype-phenotype correlation was not identified, but inter- and intrafamilial phenotypic variability was observed. Overall, these findings are similar to the results of previously conducted studies, and the mechanism underlying the phenotypic variations and predisposing factors of the development and progression of nephropathy in NPS patients are still unknown.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Primers do DNA/química , Genótipo , Proteínas de Homeodomínio/genética , Falência Renal Crônica/genética , Coreia (Geográfico) , Mutação , Síndrome da Unha-Patela/diagnóstico , Fenótipo , Fatores de Transcrição/genéticaRESUMO
Introdução: A Doença de Fabry é uma doença genética de depósito lisossômico caracterizada pela deficiência da enzima α-galactosidase A (ceramidatrihexosidase). Isso gera acúmulo de globotriaosilceramida (GL-3) no endotélio vascular, podendo ocasionar complicações renais, cardíacas ecerebrovasculares. Diante da terapia de reposição enzimática, torna-se essencial o diagnóstico desta doença, o que pode ser conseguido através de umrastreamento de pacientes em hemodiálise. Objetivos: O presente estudo objetivou determinar a prevalência da doença em pacientes portadores dedoença renal crônica em hemodiálise na cidade de Natal RN, avaliando as principais co-morbidades associadas. Métodos: Foram selecionadosindivíduos do sexo masculino em hemodiálise, entre 18 e 65 anos, excluindo-se pacientes cuja etiologia da falência renal era: diabetes mellitus, lupuseritematoso sistêmico, nefropatia obstrutiva, pielonefrite crônica e doença renal policística. Uma amostra sanguínea foi coletada para avaliação da atividadeda α-galactosidase A em papel de filtro. Os pacientes com valores inferiores a 2,5μmol/L/h tiveram a atividade enzimática testada em leucócitos eresponderam a um questionário sobre as manifestações clínicas relacionadas. Resultados: Dos 191 pacientes, 16 (8,3%) cursaram com atividadeenzimática em papel de filtro inferior a 2,5μmol/L/h. Apenas um paciente (0,52%) apresentou dosagem da atividade enzimática em leucócitos inferior aovalor da normalidade, sendo compatível com Doença de Fabry. Não foram encontradas as manifestações típicas da doença neste paciente. Conclusão:Observou-se uma prevalência da Doença de Fabry de 0,52% dentre os pacientes estudados nos centros de hemodiálise de Natal RN no ano de 2006.
Introduction: Fabry Disease is a genetic illness of lisosomic deposition characterized by the deficiency of the enzyme alpha-galactosidase A (ceramidetrihexosidase), generating an accumulation of globotriaosilceramide (GL-3) in the vascular endothelium, capable of leading to renal, cardiac andcerebrovascular complications. Faced with the therapeutic possibility of enzymatic supplementation, the diagnosis of this disease becomes essential, andcan be achieved through the screening of hemodialysis patients. Aims: The present study aimed at determining the prevalence of Fabry Disease in patientswith chronic kidney disease undergoing hemodialysis in the city of Natal, Rio Grande do Norte, Brazil, evaluating the main associated comorbidities.Methods: The sample consisted of male subjects between 18 and 65 years of age, undergoing hemodialysis, excluding patients whose etiology of renalfailure was diabetes mellitus, systemic lupus erythematosus, obstructive nephropathy, chronic pyelonephritis, or polycystic kidney disease. A blood samplewas collected for an evaluation of alpha-galactosidase A activity in filter paper. Patients with values inferior to 2.5 μmol/L/h had their enzymatic activity testedin leukocytes, and a questionnaire about related clinical manifestations was applied. Results: From 191 patients, 16 (8.3%) had an enzymatic activity infilter paper inferior to 2.5 μmol/L/h. Only one patient (0.52%) exhibited a level of enzymatic activity in leukocytes inferior to the normal value, compatible withFabry Disease. The typical manifestations of the disease were not found in this case. Conclusion: A prevalence of Fabry Disease of 0.52% was observedamong patients studied in hemodialysis centers in Natal in 2006.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Diálise Renal , Doença de Fabry/genética , Doença de Fabry/metabolismo , Falência Renal Crônica/genética , alfa-Galactosidase/análiseRESUMO
Hyperhomocysteinemia [HHcy] has recently been suggested as a risk factor for atherosclerosis [AS] in patients with chronic renal disease. Several mechanisms for HHcy-induced AS have been proposed but the molecular pathogenesis of this relation is still unclear. So far, there are no reports showing the changes in homocysteine levels in acute renal failure. We investigated whether HHcy is a common finding in acute and chronic renal failure, its relation to the pathogenesis of vascular dysfunction and its possible treatment by folic acid. 35 rats were divided into 5 groups [Gp]: Gp1 [sham operated]; Gp2 [acute ischemic renal failure]; Gp3 [treated acute ischemic renal failure]; Gp4 [chronic renal failure]; Gp5 [treated chronic renal failure]. Blood samples were collected for determination of urea, creatinine and homocysteine. Aortae were harvested for assessment of vascular endothelial growth factor [VEGF] expression and aortic content of tumor necrosis factor alpha [TNF]. Both acute [Gp2] and chronic [Gp4] models of renal failure showed higher homocysteine concentrations; increased VEGF expression and increased TNF alpha than Gpl. Folic acid treatment caused significantly lower homocysteine levels and VEGF expression in Gp3 and Gp5 than Gp2 and Gp4, while its reducing effect on TNF was only evident in acute treated model compared to Gp2. Homocysteine significantly correlates with creatinine and VEGF expression in acute models [Gp2 and 3], with urea, creatinine, TNF alpha in chronic model [Gp4] and with TNF alpha in Gp5. Our findings demonstrate that HHcy is evident in acute and chronic renal failure. Increased VEGF expression in acute failure and enhanced vascular inflammation in chronic failure could be possible mechanisms by which HHcy accelerates AS. However, the direct causal relationship between them needs further investigations. Folic acid decreases HHcy and could be useful in reducing cardiovascular risk factors in uremic patients
Assuntos
Animais de Laboratório , Injúria Renal Aguda/genética , Falência Renal Crônica/genética , Hiper-Homocisteinemia , Endotélio Vascular , Fatores de Necrose Tumoral , Fatores de Crescimento Endotelial , Homocisteína , Arteriosclerose , Ácido Fólico , Ratos , Eletroforese em Gel de Ágar , Reação em Cadeia da PolimeraseRESUMO
Patients with chronic renal insufficiency (CRI) have reduced hemoglobin levels, mostly as a result of decreased kidney production of erythropoietin, but the relation between renal insufficiency and the magnitude of hemoglobin reduction has not been well defined. Hereditary hemochromatosis is an inherited disorder of iron metabolism. The importance of the association of hemochromatosis with treatment for anemia among patients with CRI has not been well described. We analyzed the frequency of the C282Y and H63D mutations in the HFE gene in 201 Brazilian individuals with CRI undergoing hemodialysis. The analysis of the effects of HFE mutations on iron metabolism and anemia with biochemical parameters was possible in 118 patients of this study (hemoglobin, hematocrit, ferritin levels, transferrin saturation, and serum iron). A C282Y heterozygous mutation was found in 7/201 (3.4 percent) and H63D homozygous and heterozygous mutation were found in 2/201 (1.0 percent) and 46/201 (22.9 percent), respectively. The allelic frequencies of the HFE mutations (0.017 for C282Y mutation and 0.124 for H63D mutation) did not differ between patients with CRI and healthy controls. Regarding the biochemical parameters, no differences were observed between HFE heterozygous and mutation-negative patients, although ferritin levels were not higher among patients with the H63D mutation (P = 0.08). From what we observed in our study, C282Y/H63D HFE gene mutations are not related to degrees of anemia or iron stores in CRI patients receiving intravenous iron supplementation (P > 0.10). Nevertheless, the present data suggest that the H63D mutation may have an important function as a modulating factor of iron overload in these patients.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Falência Renal Crônica/genética , Proteínas de Membrana/genética , Brasil , Estudos de Casos e Controles , Genótipo , Hemocromatose/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Mutação/genética , Diálise RenalRESUMO
Glomerular filtration rate decline (GFRd) is variable in autosomic dominant polycystic kidney disease (ADPKD). In 88 ADPKD patients, GFRd was assessed by 1/S(Cr) and compared with the association to AT1A1166C (AT1R), AGTM235T (angiotensinogen) and ecNOSGlu298Asp (NO endothelial synthase) polymorphisms. Age at S(Cr) values of 2 and 6 mg/dl were assumed as beginning of progressive phase (A2) and end-stage-renal disease (A6), respectively. Polymorphisms were studied by PCR-RFLP. The group as a whole showed GFRd (ml/min/year) of 6.9+/-0.5; A2 and A6 of 48.9+/-1.3 and 55.0+/-1.4 years and mean arterial pressure of 111.2+/-1.2 mmHg. When A6 was considered, two populations were defined (< or = and > 55 years). In < or = 55 (assumed as PKD1 phenotype) (n=42), A2 and A6 of the AT1 1166CC genotype were 36.0+/-1.2 and 41.4+/-0.9 years vs AA-AC (42.8+/-1.0 and 47.5+/-0.8, p<0.001). A2 and A6 of the ecNOS298Asp/Asp genotype were 34.8+/-1.5 and 41.1+/-0.6 years vs. Glu/Glu-Glu/Asp (42.4+/-0.9 and 47.1+/-0.8, p<0.02). In AGT235TT genotype, GFRd was 12.4+/-2.2 ml/min/year vs MM-MT (7.9+/-0.7, p<0.03). This difference was also observed when all ADPKD patients were considered (TT: 11.02+/-1.5 vs. MM-MT: 6.44+/-0.5 ml/ min/year, p<0.003). AT1 1166CC and ecNOS 298Asp/Asp are associated with earlier A2 and A6 whereas AGT 235TT induce twofold increase in GFRd, suggesting that RAS and ecNOS are involved in ADPKD progression.
La velocidad de progresión (VdP) de la poliquistosis renal autosómica dominante (PQRAD) es variable.Estudiamos la asociación de los polimorfismos AGTM235T (angiotensinógeno), AT1A1166C(ATR1) y ecNOSGlu298Asp (NO sintasa endotelial) con la VdP en 88 pacientes. VdP fue estimada por 1/Crplvs edad. Consideramos edades de Crpl 2 y 6 mg/dl como comienzo de progresión (E2) y arribo a insuficienciarenal crónica terminal (E6), respectivamente. Los polimorfismos se estudiaron por PCR-RFLP. El grupo en sutotalidad presentó VdP (ml/min/año) de 6.9±0.5, E2 y E6 de 48.9±1.3 y 55.0±1.4 años y tensión arterial media(TAM) de 111.2±1.2 mmHg. Según E6 observamos dos grupos (≤ y > a 55 años). En ≤ 55 (fenotipo PKD1,n=42), E2 y E6 del genotipo CC de AT1A1166C fueron 36.0±1.2 y 41.4±0.9 años vs. AA-AC (42.8±1.0 y 47.5±0.8, p < 0.001). E2 y E6 del genotipo ecNOS298Asp/Asp fueron 34.8±1.5 y 41.1±0.6 años vs. Glu/Glu-Glu/Asp (42.4±0.9 y 47.1±0.8, p < 0.02). En el genotipo AGT235TT, la VdP fue 12.4±2.2 ml/min/año vs. MM-MT (7.9±0.7, p < 0.03). Esta diferencia también se observó cuando analizamos todos los pacientes PQRAD (TT: 11.02±1.5 vs. MM-MT: 6.44±0.5 ml/min/año, p < 0.003). Los genotipos AT1 1166CC y ecNOS 298Asp/Asp anticipan E2 y E6 mientras que AGT235TT duplica VdP, sugiriendo la participación del sistema renina angiotensina y NO sintasaendotelial en la progresión de la PQRAD.
Assuntos
Adulto , Animais , Humanos , Camundongos , Pessoa de Meia-Idade , Angiotensinogênio/genética , Falência Renal Crônica/genética , Óxido Nítrico Sintase/genética , Polimorfismo Genético , Rim Policístico Autossômico Dominante/genética , Sistema Renina-Angiotensina/genética , Progressão da Doença , Falência Renal Crônica/patologia , Genótipo , Taxa de Filtração Glomerular , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Óxido Nítrico/genética , Fenótipo , Análise de Regressão , Rim Policístico Autossômico Dominante/patologiaRESUMO
Many patients with chronic renal failure (CRF) requiring hemodialysis present with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be associated with primary HTG, atherosclerosis and coronary artery disease. This study was designed to evaluate the association between the restriction fragment length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII-AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR products by two restriction enzymes, SstI and MspI. The frequency of SstI minor allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF-NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p>0.005). These data indicate that genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the causes of HTG in CRF.
Assuntos
Feminino , Humanos , Masculino , Apolipoproteína A-I/genética , Apolipoproteínas A/genética , Apolipoproteínas C/genética , Apolipoproteínas C/sangue , Colesterol/sangue , Hipertrigliceridemia/genética , Hipertrigliceridemia/complicações , Falência Renal Crônica/genética , Falência Renal Crônica/complicações , HDL-Colesterol/sangue , Pessoa de Meia-Idade , Família Multigênica , Diálise Renal , Triglicerídeos/sangue , Variação GenéticaRESUMO
Many patients with chronic renal failure (CRF) requiring hemodialysis present with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be associated with primary HTG, atherosclerosis and coronary artery disease. This study was designed to evaluate the association between the restriction fragment length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII-AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR products by two restriction enzymes, SstI and MspI. The frequency of SstI minor allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF-NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p>0.005). These data indicate that genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the causes of HTG in CRF.