Hasmukh R. Fatania

Association of blood levels of C-reactive protein with clinical phenotypes in Arab schizophrenic patients

Schizophrenia may be associated with inflammatory reactions and C-reactive protein (CRP) is a nonspecific serum protein marker for persisting inflammatory states. This study aimed to assess concentrations of high sensitivity CRP (hsCRP) in schizophrenic Arab patients and evaluate the relationships of hsCRP levels with aspects of clinical phenotypes of the disease. Two age-matched groups of subjects were studied: (1) healthy controls, HC, n=165; (2) patients with schizophrenia, SZ: n=207. Each subject was evaluated with a standard questionnaire for age at disease onset, family history, disease severity and outcome. Serum hsCRP levels were measured by immunoassay. The two groups of subjects were similar in age, ethnic composition and socioeconomic status. Those with SZ had significantly greater serum concentrations of hsCRP. There were significant associations between hsCRP and (i) age in both groups; (ii) body mass index (BMI) in HC but not in SZ. In the latter, hsCRP levels were: (a) marginally higher in women with later age of disease onset; (ii) highest with remission and with catatonic features; and (iii) lower with family history of psychosis. The study concludes that serum levels of hsCRP are increased in clinically stable Arab patients with schizophrenia and appear related to the disorders clinical expression. It is suggested that there may be an inflammatory component to schizophrenia which is associated with aspects of its clinical phenotype.

Purification and partial characterisation of NADP+‐linked isocitrate dehydrogenase from rat liver cytosol

NADP+‐linked isocitrate dehydrogenase from rat liver cytosol was purified (approximately 135‐fold) to apparent homogeneity in 27% yield. The purified enzyme has specific activity of 73 units · mg− 1. The native enzyme showed an apparent M r of 94,000 by gel filtration and was composed of two identical subunits of M r 45,000 as judged by SDS/PAGE. In isoelectric focusing, a pI value of 5.7 was estimated for the enzyme.

Chemical modification of rat liver cytosolic NADP+-linked isocitrate dehydrogenase by N-ethylmaleimide Evidence for essential sulphydryl groups

Incubation of rat liver cytosolic isocitrate dehydrogenase with N‐ethylmaleimide (NEM) resulted in the inactivation of the enzyme following pseudo‐first order kinetics. Isocitrate affords considerable protection against inactivation whereas NADP+ enhances modification of the enzyme, suggesting localization of the modified group at the active site. Correlation of loss of activity with incorporation of [14C]NEM indicated that two sulphydryl residues/sub‐unit are modified of which only one is shown to be involved in catalysis. pH dependence of the inactivation process implicates a reactive group of pK a 8.1 in catalysis. We conclude that a unique cysteine residue is essential for maximal catalytic activity of isocitrate dehydrogenase.

Apolipoprotein E Polymorphism and Clinical Disease Phenotypes in Arab Patients with Schizophrenia

Background: Apolipoprotein E (APOE) is polymorphic, and may be involved in the pathogenesis and clinical expression of schizophrenia. This study aimed to investigate the frequency of specific APOE genotypes and alleles in a schizophrenic Arab population and evaluate the association of specific APOE types with clinical phenotypes of the disease. Subjects and Methods: Two age-matched groups of subjects were studied: (1) healthy controls, n = 165; (2) patients with schizophrenia (SZ), n = 207. Each subject was evaluated for age and mode of onset of disease, family history of psychosis, disease severity and outcome over the years of illness. APOE genotyping was performed by a validated PCR-RFLP technique. Results and Discussion: Genotype E3E2 and allele E2 were less frequent in the patients with schizophrenia (p = 0.04), and both APOE types tended to be more common in male than female schizophrenic patients (p = 0.08). Schizophrenic patients with a positive family history of psychosis had lower frequencies of genotype E3E2 and allele E2 (both p = 0.04). Genotype E3E4 and allele E4 were least common in patients with an age at onset of disease >31 years (OR: 5.5, 95% CI: 1.1–27.4), particularly in males. Conclusion: APOE genetic polymorphism potentially influences susceptibility to schizophrenia and may be associated with aspects of its phenotypic expression, particularly gender, age of onset and family history of psychotic illness. This relationship of APOE with schizophrenia is likely to be race- and gender-specific.

Associations of blood levels of insulin-like growth factor (IGF)-I, IGF-II and IGF binding protein (IGFBP)-3 in schizophrenic Arab subjects

BACKGROUND Insulin-like growth factors (IGFs) are believed to be important in brain development and repair following neuronal damage. It is also speculated that IGFs are involved in the association of foetal and pre-adult growth with schizophrenia (SZ). METHODS The aim of this study was to assess levels of IGF-I, IGF-II and IGF binding protein (IGFBP)-3 and their associations in male Arab patients with SZ (n=53) and healthy control subjects (HC; n=52). Anthropometric and demographic data were collected for each subject for whom blood specimens were analysed for serum lipoproteins, apolipoprotein B (apoB), IGF-I, IGF-II and IGFBP-3. RESULTS The SZ group had lower serum total cholesterol, apoB and uric acid levels than the HC group (p<0.05). IGF-II levels were significantly higher in the SZ group (p=0.02) and correlated positively with levels of atherogenic lipoproteins--total cholesterol, low-density lipoprotein, apoB--and IGFBP-3. The pattern of correlations between the IGFs and the various parameters differed somewhat between the HC and SZ groups. CONCLUSIONS These results demonstrate that IGF-II levels are increased in patients with SZ and show significant associations with atherogenic lipoproteins. We suggest a possible link between IGF-II metabolism and atherogenesis in SZ.

Analysis of the D1S80 (pMCT118) VNTR locus polymorphism in a native Kuwaiti population by the polymerase chain reaction

We have determined the allele and genotype frequencies at the hypervariable locus D1S80 in a native Kuwaiti population using the polymerase chain reaction technique and subsequent high resolution gel electrophoresis. In a sample of 200 individuals, 21 alleles and 57 genotypes were detected. The alleles with 18 and 24 repeat units were most common with frequencies of 0.188 and 0.408 respectively. The distribution of the observed genotypes was in agreement with the Hardy-Weinberg equilibrium prediction. The observed heterozygosity for the population sample was 0.80 with the allelic diversity of 0.781 +/- 0.029 and the power of discrimination was 0.94. The data obtained in this study are potentially useful for individual identification in forensic casework.

HLA-DQα allele and genotype frequencies in a native Kuwaiti population

Abstract We report the allele and genotype frequencies in a sample of an unrelated native Kuwaiti population determined by the use of polymerase chain reaction (PCR) and reverse dot-blot analysis. This technique, involving the use of commercially available AmpliType HLA-DQα forensic DNA amplification and typing kit, has permitted the definition of six alleles and 21 genotypes in a sample of 220 people. The allelic frequencies are in the range 5.7–27.5%. This locus demonstrated a heterozygosity of 0.80 with an allelic diversity of 0.81 and the power of discrimination (PD) was 0.93. The distribution of observed genotypes conformed to Hardy-Weinberg equilibrium thus indicating genetic equilibrium of the different variants. This population data should permit the use of HLA-DQα marker for individual identification in forensic casework.