title: High expression of TNF alpha is associated with -308 and -238 TNF alpha polymorphisms in knee osteoarthritis.
abstract: Knee osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage components due to an imbalance between extracellular matrix destruction and repair. The proinflammatory cytokines involved in OA, TNFα and IL1β, are considered the major implicated. The aim of this study was to investigate the relationship between TNFα -308 and -238 polymorphisms with messenger RNA (mRNA) and soluble TNFα expression in knee OA patients and healthy subjects (HS). Case-control study involved 50 knee OA patients classified according to 1986 ACR Classification Criteria, as well as 100 HS. The Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne disability index were applied to OA patients. The -308 and -238 polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism technique. The TNFα mRNA expression was quantified by real-time PCR using TaqMan method. The sTNFα levels were measured by enzyme-linked immunosorbent assay. The TNFα mRNA expression in knee OA patients was higher than in HS (1.56-fold). In addition, the TNFα mRNA expression was higher in carriers of G allele in the knee OA group for both polymorphisms. The sTNFα levels were increased in G/G versus G/A genotypes in both studied polymorphisms (p < 0.05). However, the TNFα -308 and -238 genotypes did not show statistical differences between groups. The G allele of TNFα -308 and -238 polymorphisms is associated with high mRNA and soluble expression in knee OA patients. However, it is not a marker of susceptibility in Western Mexico. Further studies are necessary to confirm these findings.
authors.affiliation: Grupo de Inmunogenética Funcional, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Insurgentes 244-1, Colonia Lomas de Atemajac, C.P. 45178, Zapopan, Guadalajara, Jalisco, Mexico, biologiamolecular@hotmail.com.
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Muñoz-Valle
authors.forename: Edith
authors.initials: E
authors.lastname: Oregón-Romero
authors.forename: Héctor
authors.initials: H
authors.lastname: Rangel-Villalobos
authors.forename: Gloria Esther
authors.initials: GE
authors.lastname: Martínez-Bonilla
authors.forename: Eduardo
authors.initials: E
authors.lastname: Castañeda-Saucedo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Salgado-Goytia
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Leyva-Vázquez
authors.forename: Berenice
authors.initials: B
authors.lastname: Illades-Aguiar
authors.forename: Luz del Carmen
authors.initials: Ldel C
authors.lastname: Alarcón-Romero
authors.forename: Mónica
authors.initials: M
authors.lastname: Espinoza-Rojo
authors.forename: Isela
authors.initials: I
authors.lastname: Parra-Rojas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D009864:Ontario; D020370:Osteoarthritis, Knee / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D050436:Regulatory Elements, Transcriptional; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha