Gonenc Kocabay

Impact of apolipoprotein E genotypes on phenotypic expression in Turkish patients with Wilson's disease

TO THE EDITOR: Wilson’s disease (WD) is a disorder characterized by excessive hepatic copper accumulation and impaired biliary copper excretion. This accumulation can result in severe neurological symptoms and liver disease. The wide spectrum of phenotypic features in WD cannot be predicted. In a study about the effects of ApoE genotypes on WD it is reported that onset was significantly delayed with ApoE o3/3 [1]. We sought to determine the feature of disease at presentation and ApoE genotype in Turkish patients with WD. Fifty-six patients (21 F, 35 M) with symptomatic WD were recruited and classified according to symptoms at presentation as either neurological or hepatic. WD was diagnosed on the basis of typical symptoms and the presence of biochemical indicators (plasma ceruloplasmin B200 mg/l, serum copper B10 mmol/l, liver copper concentrations 250 mg/g on biopsy). All patients were examined for the presence of Kayser-Fleischer rings in the cornea on split lamp examination. WD phenotype was classified according to the international consensus classification [2]. The neurological examination resembled the scoring system published by Oder et al. [3]. At least two neurological symptoms were diagnosed as neurological involvement, while liver involvement was assessed by liver function tests, ultrasonography and liver biopsy. The ApoE genotype was determined by polymerase chain reaction (PCR) using the ApoE amplification kit. In humans, the structural gene locus for plasma apolipoprotein E is polymorphic. Three common alleles, designated as o2, o3 and o4, code for three major isoforms in plasma designated as apoE2, apoE3 and apoE4, respectively. After amplification of the ApoE o alleles, genotyping was performed using a reverse hybridization technique. SPSS for Windows software version 13.0 was used for statistical analysis. Statistical analysis was performed using the x test. The criterion for statistical significance was pB0.05. Frequencies of ApoEo3 and ApoEo4 alleles in WD were not significantly different from those in controls (96 healthy persons, 43 F, 53 M) (x 0.08 and 0.31, respectively, both p 0.05). Of the 56 patients (21 F, 35 M) with symptomatic WD, 28 patients presented with neurological symptoms and 28 with hepatic symptoms. The distribution of ApoE genotypes in WD is ApoEo3/3 80.4%, o3/4 8.9%, o2/3 10.7%, o4/4 4.1%. None of our patients had the allele combinations ApoEo2/2 and o2/4. There were no significant differences in ApoE alleles and phenotypic features (either neurologic or hepatic) (Table I) (ApoEo2, x 0.39; ApoEo4, x 0.64). According to the gender classification of patients with WD, it was found that the hepatic phenotypic features were more common in female patients (n 14, 66%), whereas the neurologic phenotypic features were more common in the male patients (n 21, 60%) ( p 0.053 for both). The presence of Kayser-Fleischer rings is associated with the neurologic phenotype (x, p 0.01, Table I). The relation between Kayser-Fleischer rings and ApoE genotypes is not significantly different (ApoEo2 and ApoEo4, respectively p 0.50, p 0.90). The frequency of ApoE genotypes in Turkish patients with WD was not significantly different

Suicide attempt with clopidogrel

We report the case of a 49-year-old male who took an overdose of 1650 mg of clopidogrel with suicidal intend. The patient developed abnormalities of platelet aggregation, but never developed symptoms. Clopidogrel is a commonly prescribed drug. Reports of overdose of clopidogrel were very rarely reported in the literature.