Apolipoprotein E polimorfizminin son dönem böbrek yetmezliğinde serum lipid ve lipoproteinleri üzerine etkisi

Abstract

ÖZET Lipid ve lipoproten bozuklukları SDBYde sık görülür. Anormal lipid metabolizması böbrek hastalığının ilerlemesine eşlik edebilir. Yapılan çalışmalar göstermiştir ki Apo-E lipoprotein metabolizmasında ve apo-E fenotipine göre lipoprotein katabolizmasını etkileyerek önemli bir rol oynar. Apo-E allele sıklığı ırklar arasında farklılık gösterir. Apo-E polimorfîzmi üç önemli allele içerir (EZ, E3 ve E4). Apo-E1 de görülen bu polimorfîzm genel populasyonda ateroskleroz morbiditesini etkilediği rapor edilmiştir. Biz çalışmamızda Apo-E allele ve fenotipe sıklığının belirlenmesi, belirlenen polimorfizmlerin SAPD ve HD hasta gruplarında lipid profilleri üzerine etkisini araştırdık. Metod: Apo-E fenotipi 52 sağlıklı kontrol, ve 144 SDBY'likli (72 HD, 72 SAPD) hastalarda polimeraz zincir reaksiyonu ile belirlendi. Allel sıklığı ve fenotipe dağılımı `gen counting` metodu kullanılarak hesaplandı. Lipid ve lipoprotein değerleri en az 12 saatlik açlığı takiben ölçülmüştür. Sonuç: Apo-E allel ve fenotipe dağılımı SAPD, HD ve kontrol grupları arasında benzer bulunmuştur. Farklı etiolojilerdeki SDBYde apo-E fenotipe dağılımı benzerdi. HD hasta grubunda T-kolesterol, LDL-Kolesterol, apo-B serum düzeyleri SAPD ve kontrol grubuna göre anlamlı derecede düşük bulundu. SAPD,HD hastalarınm apo-E fenotip subgrup T-kolesterol, LDL-Kolesterol, HDL-kolesterol, TG, apo-B, apo-A, Lpa düzeyleri kontrol grubu ile benzerdir. ESRD hasta grubunda E3E4 fenotipinde total kolesterol (206 ± 58 vs 167 ± 35 mg/dl) ve apo-B (1.04 ± 0,34 vs 0.82 ± 0.24 mg/dl) düzeyleri E2E3 fenotipinden yüksek bulunmuştur (p<0.05). LDL-Kolesterol E3E3 fenotipinde E2E3fenotipinden yüksekti (110 ± 38 vs 89 ± 36mg/dl, p<0.05). hemodiyaliz hastalarında E3E4 fenotipinde hem total kolesterol (223 ± 85 vsl54 ± 23 mg/dl) hemde LDL-kolesterol (125 ± 78 vs 77 ± 30mg/dl) E2E3 fenotipinden istatistiksel olarak anlamlı yüksek bulundu (p<0.05) Total kolesterol ve Trigliserid düzeyleri E3E4 50fenotipinde (223 ± 85 ve 326 ± 210) E3E3 fenotipinden (167 ± 39 ve 185 ± 130) yüksekti. (p<0.05). Apo-B benzer şekilde E3E4 fenotipinde (1.1 ± 0.47mg/dl) E2E3 fenotipinden (0.72 ± 0.2mg/dl) yüksekti (p<0.05) SAPD ve kontrol grubunda apo-E fenotype dağılımı ile lipid parametreleri arasında belirgin bir korelasyon saptanmamıştır. Multiple lojistik regresyon analizinde sadece yaş aterosklerozda bağımsız risk faktörü olarak bulunurken apo-E fenotip dağılımı ile bu ilişki gösterilememiştir. Tartışma: Apo-E fenotipi coğrafi dağılımı Türk toplumunda Akdeniz toplumu ile uygunluk göstermektedir. Apo-E fenotipe dağılımı ESRD için genetik bir yatkınlık oluşturmamaktadır. E3E4 fenotipindeki Total ve LDL-kolesterol yüksekliği tespit edilmesine rağmen çalışmamızda T-kolesterol, LDL-Kolesterol ve apo-E fenotipi ateroskleroz için bağımsız risk faktörü olarak gösterilememiştir 51

ABSTRACT Backgrounds. Lipid and lipoprotein abnormalities are frequently found in end-stage renal disease (ESRD) patients, and abnormal lipid metabolism may contribute to the progression of renal disease. Previous investigators have reported that apolipoprotein-E (apo- E) has an important role in lipoprotein metabolism and that the process of lipoportein catabolism varies according to the apo-E phenotypes. In addition, the relative frequency of the apo-E alleles was found to be different among the races. Apo-E polymorphism consists of tree major alleles (E2, E3 and E4). Because of their difference in a lipid-modulating effect, the polymorphism has been reported to affect the progresion and morbidity of atherosclerosis in generel population. In this study, we investigated the allele frequency of apo-E phenotypes and evaluated the impact of apo-E polymorphism on lipid profile and atherosclerosis in Turkish hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. Methods; Apo-E phenotypes were determined by polymerase chain reaction in 144 Turkish ESRD patients (72 HD, 72 CAPD) and 52 healthy controls. The allele frequency and apo-E phenotype distribution were estimated by the gene-counting method. Serum lipid parameters were measured after a 12-hour fasting period. Result; We found a similar phenotype distribution and allele frequency among HD, CAPD and healthy controls. The distributions of Apo-E phenotypes were similar among the different etiologies of ESRD. Total cholesterol (T-Chol), LDL-cholesterol (LDL-Chol) and apolipoprotein-B (apo-B) levels were significantly lower in HD patient compaired to CAPD and control groups. When analysed together, all phenotypes of apo-E in CAPD and HD patients had statisticlly similar T-Chol, LDL-Chol, apo-B, HDL-Cholesterol (HDL-Chol), triglyseride (TG), apolipoprotein-A (apo-A), lipoprotein (a) (Lpa) levels compaired to that of control group. T-Chol levels in E3E4 phenotypes of ESRD patients were significantly higher than that of E2E3 phenotypes (206 ± 58 mg/dl vs 167 ± 35 mg/dl; p<0.05). Similarly apo-B 48levels in E3E4 phenotypes of ESRD patients were significantiy higher than that of E2E3 phenotypes (1.04 ± 0,34 g/L vs 0.82 ± 0.24 g/L, p<0.05). LDL-Chol levels were also higher in E3E3 phenotypes compared to E2E3 phenotypes in ESRD patients (110 ± 38 mg/dl vs 89 ± 36mg/dl; p<0.05). In HD patients, T-Chol level in E3E4 phenotypes was significantly higher than that of E2E3 phenotype (223 ±85 mg/dl vs 154 ± 23 mg/dl; p<0.05). Similarly; LDL-Chol level was significantly higher in E3E4 phenotype compared to E2E3 phenotype (125 ± 78 mg/dl vs 77 ± 30 mg/dl; p<0.05). T-Chol and TG levels in E3E4 phenotype was significantly higher than that of E3E3 phenotypes in HD patients (p<0.05). Apo-B levels in E3E4 phenotype of HD patients were significantly higher than that of E2E3 phenotype (1.1 ± 0.47 g/L vs 0.72 ± 0.2 g/L; p<0.05). Lipid parameters of all phenotypes in CAPD patiens and control group were similar. Multiple logistic regression analysis revealed that age was the only independent risk factors for atherosclerosis. Conclusions: Distribution of apo-E phenotypes was in ESRD patients and healthy controls. Although, T-Chol and LDL-Chol levels were sinficanly higher in E3E4 phenotype, we could not demonstrate T-Chol, LDL-Chol or any of apo-E phenotypes as an independent risk factor for atherosclerosis in our study population. 49