title: Characterization of HPSE gene single nucleotide polymorphisms in Jewish populations of Israel.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunobiology, Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel. olga.ostrovsky@sheba.health.gov.il
authors.forename: Olga
authors.initials: O
authors.lastname: Ostrovsky
authors.forename: Michael
authors.initials: M
authors.lastname: Korostishevsky
authors.forename: Iris
authors.initials: I
authors.lastname: Levite
authors.forename: Merav
authors.initials: M
authors.lastname: Leiba
authors.forename: Hanan
authors.initials: H
authors.lastname: Galski
authors.forename: Ephraim
authors.initials: E
authors.lastname: Gazit
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000352:Africa, Northern / Q000208:ethnology; D019943:Amino Acid Substitution; D005060:Europe / Q000208:ethnology; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D005966:Glucuronidase / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D015810:Linkage Disequilibrium; D019083:Mediterranean Region / Q000208:ethnology; D008877:Middle East / Q000208:ethnology; D020125:Mutation, Missense; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase