title: Association of ENPP1 gene polymorphisms with hand osteoarthritis in a Chuvasha population.
abstract: Periarticular calcification is a common attendant symptom of generalized arterial calcification of infancy, a rare Mendelian disorder caused by mutations of the gene coding for ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). This prompted us to perform a family-based association study to test the hypothesis that genetic variation at the ENPP1 locus is involved in the etiology of osteoarthritis of the hand. The study population comprised 126 nuclear families with 574 adult individuals living in small villages in the Chuvasha and Bashkirostan autonomies of the Russian Federation. The extent of osteoarthritis was determined by analyzing plain hand radiographs. The outcome of a principal component analysis of osteoarthritis scores of a total of 28 joints of both hands was used as a primary phenotype in this study. Maximum likelihood estimates of the variance component analysis revealed a substantial contribution of genetic factors to the overall trait variance of about 25% in this homogeneous population. Three short tandem repeat (STR) polymorphisms--one intragenic and two flanking markers--and four single-nucleotide polymorphisms were tested. The markers tagged the ENPP1 locus at nearly equal intervals. We used three different transmission disequilibrium tests and obtained highly significant association signals. Alleles of the upstream microsatellite marker as well as several single-nucleotide polymorphism haplotypes consistently revealed the association. Thus, our data highlights variability of ENPP1 as an important genetic factor in the pathogenesis of idiopathic osteoarthritis.
authors.affiliation: Gene Mapping Center, Max Delbrück Center for Molecular Medicine, Berlin, Germany. anitasuk@aol.com
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Suk
authors.forename: Ida
authors.initials: I
authors.lastname: Malkin
authors.forename: Stefan
authors.initials: S
authors.lastname: Dahm
authors.forename: Leonid
authors.initials: L
authors.lastname: Kalichman
authors.forename: Nico
authors.initials: N
authors.lastname: Ruf
authors.forename: Eugene
authors.initials: E
authors.lastname: Kobyliansky
authors.forename: Mohammad
authors.initials: M
authors.lastname: Toliat
authors.forename: Frank
authors.initials: F
authors.lastname: Rutsch
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Gregory
authors.initials: G
authors.lastname: Livshits
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001486:Bashkiria / Q000453:epidemiology; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003460:Crystallization; D011756:Diphosphates / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D050276:Hand Bones / Q000000981:diagnostic imaging / Q000473:pathology*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000208:ethnology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics / Q000502:physiology*; D011859:Radiography; D012045:Regulatory Sequences, Nucleic Acid; D012426:Russia / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D011756:Diphosphates; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases