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Michael Korostishevsky

Publications and source records attributed to Michael Korostishevsky.

8 recordsLinked to original sources
PubMed2006

Characterization of HPSE gene single nucleotide polymorphisms in Jewish populations of Israel.

Heparanase is a mammalian endoglucuronidase responsible for heparan sulfate (HS) degradation. HS is a major constituent of the extracellular matrix (ECM) and HS-degrading activity plays a decisive role in fundamental biological processes associated with remodeling of the ECM, such as cancer metastasis, angiogenesis and inflammation. There is great interest in the prospect of genome-wide association studies to identify genetic factors underlying complex diseases. It is important to establish a detailed description of the heparanase (HPSE) gene single nucleotide polymorphisms (SNPs). In this study, four Israeli Jewish populations (Ashkenazi, North African, Mediterranean and Near Eastern) were examined for 7 HPSE gene SNPs. Four out of 7 SNPs (rs4693608, db11099592, rs4364254, db6856901) were found to be polymorphic. Population comparisons revealed significant differences in SNPs allele frequency between Near Eastern and each of the other three populations. Genotype and allele frequencies in Jewish populations were different from non-Jewish populations, except for a certain similarity to Caucasians. Although the distance between SNPs is relatively small, the db11099592 SNP was in linkage disequilibrium (LD) only with the proximal SNP rs4693608. LD between distal SNPs rs4364254 and db6856901 was found only in Mediterraneans and North Africans. The current study provides a characterization of the normally occurring HPSE gene SNPs in different populations. This information is obligatory for further studies on the linkage between these SNPs and heparanase expression and function in various pathological processes, primarily cancer progression.

Africa, Northern↗
PubMed2006

Association of the low-activity COMT 158Met allele with ADHD and OCD in subjects with velocardiofacial syndrome.

Velocardiofacial syndrome (VCFS) is caused by a microdeletion in chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. The catechol-O-methyltransferase (COMT), residing in the 22q11.2 microdeletion region, is a major candidate gene for genetic susceptibility to neuropsychiatric disorders in VCFS. Individuals with VCFS carrying the low-activity allele (COMTL) are expected to have the lowest possible COMT activity since they have only a single copy of the gene. We explored the possibility that COMTL is associated with psychiatric disorders commonly found in VCFS. Fifty-five unrelated individuals with VCFS underwent psychiatric evaluation and were genotyped for the COMT 158Val/Met polymorphism coding for COMT high/low-activity alleles. The COMTL allele was significantly more prevalent in VCFS subjects with attention deficit hyperactivity disorder (ADHD) (73.9% vs. 33.3%, OR 5.67, chi2=7.76, p=0.005) and obsessive-compulsive disorder (OCD) (78.6% vs. 33.3%, OR 7.33, chi2=7.24, p=0.007) than in the control group (VCFS subjects without OCD, ADHD and schizophrenia/schizoaffective (SZ/SZaff) disorder). The results of this study suggest that greatly reduced COMT activity, as expected in VCFS COMTL individuals may be a risk factor for psychiatric sequelae in this population. Future longitudinal studies focusing on additional COMT polymorphic sites and other candidate genes from the deleted region will elucidate the molecular pathways leading to schizophrenia and other psychiatric disorders in VCFS.

Adolescent↗
PubMed2006

Pemphigus vulgaris is associated with the transporter associated with antigen processing (TAP) system.

Pemphigus vulgaris (PV) is a human leukocute antigen (HLA) class II-associated autoimmune disease of the skin of unknown etiology. We recently described the association of pemphigus vulgaris with two clusters of microsatellite loci within the major histocompatibility complex region. One cluster includes the microsatellite marker TAP1CA, located in proximity to the transporter associated with antigen processing (TAP) genes. These genes are essential for class I antigen processing machinery and could be an additional set of genes involved in susceptibility to PV. The aim of this study was to investigate a possible association between TAP gene polymorphisms and PV. For this purpose we examined 37 unrelated Jewish Israeli patients with PV and compared them with 37 healthy Israeli Jewish HLA-matched controls. Significant differences were detected in TAP2 amino acid residues (p=0.001). Two PV TAP2 risk alleles were identified (TAP2*C and TAP2*D), the frequency of which was estimated to be 37.8% in the patients and 5.3 % in the controls. This association was found to be independent of HLA-DR. It is therefore likely that TAP2 genes are involved in susceptibility to development of PV.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Is the G72/G30 locus associated with schizophrenia? single nucleotide polymorphisms, haplotypes, and gene expression analysis.

BACKGROUND: The genes G72/G30 were recently implicated in schizophrenia in both Canadian and Russian populations. We hypothesized that 1) polymorphic changes in this gene region might be associated with schizophrenia in the Ashkenazi Jewish population and that 2) changes in G72/G30 gene expression might be expected in schizophrenic patients compared with control subjects. METHODS: Eleven single nucleotide polymorphisms (SNPs) encompassing the G72/G30 genes were typed in the genomic deoxyribonucleic acid (DNA) from 60 schizophrenic patients and 130 matched control subjects of Ashkenazi ethnic origin. Case-control comparisons were based on linkage disequilibrium (LD) and haplotype frequency estimations. Gene expression analysis of G72 and G30 was performed on 88 postmortem dorsolateral prefrontal cortex samples. RESULTS: Linkage disequilibrium analysis revealed two main SNP blocks. Haplotype analysis on block II, containing three SNPs external to the genes, demonstrated an association with schizophrenia. Gene expression analysis exhibited correlations between expression levels of the G72 and G30 genes, as well as a tendency toward overexpression of the G72 gene in schizophrenic brain samples of 44 schizophrenic patients compared with 44 control subjects. CONCLUSIONS: It is likely that the G72/G30 region is involved in susceptibility to schizophrenia in the Ashkenazi population. The elevation in expression of the G72 gene coincides with the glutamatergic theory of schizophrenia.

Adolescent↗
PubMed2004

Genotype and allele frequencies of C3435T polymorphism of the MDR1 gene in various Jewish populations of Israel.

The human multidrug-resistant gene (MDR1) encodes for P-glycoprotein (P-gp), which is a membrane-bound efflux-transporter conferring resistance to a number of natural cytotoxic drugs and potentially toxic xenobiotics. The wobble C3435T polymorphism at exon 26 was associated with different expression levels of the MDR1 gene and substrate uptake. Differences in allele frequencies of the C3435T polymorphism have previously been demonstrated between racial groups. In this study, 500 individuals from 5 Jewish populations of Israel (Ashkenazi, Yemenite, North African, Mediterranean, Near-Eastern) were examined for C3435T polymorphism using a PCR-RFLP-based technique to calculate genotype and allele frequencies. Frequencies of the C allele were quite similar among the Ashkenazi (0.65), Yemenite (0.645), and North-African (0.615) Jewish populations. However, the frequency of this allele was slightly lower among Mediterranean Jews (0.58) and significantly lower among Near-Eastern Jews (0.445). The frequency of the C allele among Near-Eastern Jews is, therefore, significantly different from those of all other tested Jewish populations. In comparison to previously studied non-Jewish populations, the frequency of this allele among Near-Eastern Jews is different from that in West Africans (0.91) but is similar to that in whites (0.497). However, the C allele frequencies among the other 4 Jewish populations are significantly lower than that found among West Africans and significantly higher than among non-Jewish whites. These data may have important therapeutic and prognostic implication for P-gp-related drug dosage recommendation in Jewish populations.

Adolescent↗
PubMed2003

Erroneous identification in a mixed population: simulation using Israeli STR data.

Allele distributions of 10 short tandem repeat (STR) polymorphic DNA loci used in forensic and paternity testing were determined for a cohort comprising 163 individuals representing a mixed Jewish Caucasian population. Typing was carried out by the commercial AmpF lSTR SGM Plus kit. The polymorphism and the utility of three of these markers for forensic studies in Israel were established for the first time. Results were compared with data for U.S. Caucasians and African Americans. The probability of identity of two persons of different ethnic origins for identification purposes is discussed. A lemma is presented to show that the chance of erroneous identification of an innocent person who belongs to a population that had not committed a crime will, in most cases, be smaller than for those who belong to a population that had truly committed the crime.

Black or African American↗
PubMed2003

Pemphigus vulgaris in Jewish patients is associated with HLA-A region genes: mapping by microsatellite markers.

Pemphigus vulgaris (PV) is the most severe autoimmune blistering disorder of the skin that is mediated by circulating autoantibodies against desmoglein 3 (Dsg3). It has been reported that in Jews the associated haplotype in PV is human leukocyte antigen (HLA) B38, DRB1*0402, DQB1*0302. Significant associations with HLA were observed also in non-Jews. Dsg3-specific T-cell responses were detected in PV patients but also in healthy individuals who were either carriers of the PV-associated DRB1*0402 allele or alleles that share similar or identical peptide binding motifs to DRB1*0402. This suggests that genes other than the classical major histocompatibility complex (MHC) genes are associated with the development of the autoimmune response. We used 16 microsatellite probes that span the entire MHC region to screen DNA samples from 38 PV patients and 76 healthy controls. Results demonstrated that some markers were associated with class II region including a TAP associated marker. However, four probes, D6S265, C_527, D6S510, and MOGC, which are all mapped to the region of HLA-A, were highly associated with PV. These results suggest that a gene, or genes in the class I region are important in the initiation of the autoimmune cascade. Activation/suppression of these genes might act as the trigger mechanism that starts the autoimmune destructive process.

ATP Binding Cassette Transporter, Subfamily B, Mem↗