title: The NOS3 (27-bp repeat, intron 4) polymorphism is associated with susceptibility to osteomyelitis.
abstract: Cytokines generate nitric oxide (NO) in osteoblasts and neutrophils through the induction of NO synthase isoforms, endothelial (NOS3) and inducible (NOS2), thereby producing bone loss. In osteomyelitis (OM), a chronic infection of the bone, homozygosity for the NOS3 (27-bp repeat, intron 4 polymorphism) 4 allele was significantly more frequent among the 80 patients than in 300 healthy controls (p=0.044). No significant differences were found for other polymorphisms of the NOS genes such as NOS3, the promoter (-786T/C), and the missense change (E298D) in exon 7, and for NOS2, the G/A substitution at position 37498 in exon 22, the (CCTTT)(n), and (TAAA)(n) micro-satellites and the -954G/C in the promoter. Serum NO levels were significantly higher only in the OM patients homozygous for the NOS3 (27-bp repeat, intron 4 polymorphism) 4 allele, compared to controls. In the presence of bacteria or bacterial products, the neutrophils of these patients produced more NO. However, immunolabelling of osteoblasts for NOS3 in biopsy tissues did not correlate with the carriage of a determined NOS polymorphism but with the presence of bone inflammation. This is the first report of an association between a NOS3 polymorphism and the risk of developing OM.
authors.affiliation: Infectious Diseases Unit, Hospital Central de Asturias, Oviedo University Medical School, Celestino Villamil s/n, 33006 Oviedo, Spain. vasensia@medynet.com <vasensia@medynet.com>
authors.forename: Victor
authors.initials: V
authors.lastname: Asensi
authors.forename: A Hugo
authors.initials: AH
authors.lastname: Montes
authors.forename: Eulalia
authors.initials: E
authors.lastname: Valle
authors.forename: Marcos G
authors.initials: MG
authors.lastname: Ocaña
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Esteban
authors.initials: E
authors.lastname: López-Anglada
authors.forename: Angeles
authors.initials: A
authors.lastname: Solís
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Alvaro
authors.initials: A
authors.lastname: Meana
authors.forename: Pelayo
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Jose A
authors.initials: JA
authors.lastname: Carton
authors.forename: Jose
authors.initials: J
authors.lastname: Paz
authors.forename: Joshua
authors.initials: J
authors.lastname: Fierer
authors.forename: Antonio
authors.initials: A
authors.lastname: Celada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001706:Biopsy; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D009573:Nitrites / Q000097:blood; D010019:Osteomyelitis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic
chemical_list: D017931:DNA Primers; D009566:Nitrates; D009573:Nitrites; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III