POLIMORFISMUL APOPROTEINEI E LA PACIENŢII CU BOALĂGAUCHER TIP I.

Introduction. Apolipoprotein E plays a crucial role in Gaucher disease's pathogenesis. Materials and Methods. The aim of our study was to identify the allelic variants of apolipoprotein E (ApoE) gene in Romanian type 1 Gaucher disease patients. Fourtyone patients, 31 receiving enzyme replacement therapy (group A) and 10 untreated (grup B) were analized. Plasma levels of total cholesterol, HDL, LDL-cholesterol, triglycerides and apolipoprotein E were determined by enzymatic methods. 41 patients have been also genotyped for ApoE polymorphism by PCR-RFLP. Results. Globally, three genotypes were identified: ϵ3/ϵ3, ϵ3/ϵ4 and ϵ2/ϵ3 in 75.6%, 14.6% and respectively 9.8% of the patients. The plasma level of Apo E was increased up to 6.20+3.86 x ULN (upper limit normal) globally (A+B), but values were different depending on the genotype: lower for genotype ϵ3/ϵ4 (3.06+1.81xULN), compared with ϵ3/ϵ3 (6.80+4.11xULN) and ϵ2/ϵ3 (6.26+1.15xULN) (p<0.05 for each). Triglycerdemia in patients carrying genotype ϵ2/ϵ3: 1.15+0.39 x ULN was superior than the values determined for genotype ϵ3/ϵ4: 0.81+0.26 (p>0.05) and for genotype ϵ3/ϵ3: 0.70+0.30 x LSN (p<0.05). The same trend of variation for ApoE and triglycerides depending onto genotype maintained similarly within group A. Plasma level of ApoE significantly correlated with triglyceridemia for all three genotypes r=0.57; 0.72; 0.85, respectively for ϵ3/ϵ3, ϵ3/ϵ4 and ϵ2/ϵ3. ERT, for 3 years, has the following consequences: decreasing level of ApoE from 8.61+6.0x to 5.42 +2.56 xULN (p >0.05), globally, in A+B; decreasing triglyceridemia - reaching the significance point for carriers of ϵ3/ϵ3 allelas - from 0.93+0.30 xULN to 0.61+0.25xULN and increasing HDL-cholesterol from 0.86+0.5x to 1.31+0.32 x LLN (lower limit normal) (p<0.05), globally, in A+B. Conclusion. This study reports the allela distibution of ApoE gene in patients with Gaucher disease, compared with general population. Plasma levels of ApoE are significantly raised and still remain high after 3 years of ERT, correlated with triglyceridemia, for all genotypes. The presence of ϵ4 allela does not results in dyslipidemic changes in treated patients, but presence of ϵ2 allela induces hypertriglyceridemia. [ABSTRACT FROM AUTHOR]