title: Polymorphic variation of hypoxia inducible factor-1 A (HIF1A) gene might contribute to the development of knee osteoarthritis: a pilot study.
abstract: BACKGROUND
  Osteoarthritis (OA) is a multifactorial degenerative condition of the whole joint with a complex pathogenesis whose development and progression is significantly mediated by interactions between the joint cartilage and articular tissues, particularly, proinflammatory mediators and oxidative stress, which results in cartilage deterioration and subchondral bone destruction. HIF-1 alpha regulates oxygen homeostasis in hypoxic tissues such as joint cartilage; efficiency of transcriptional activity of the HIF1A gene is strongly influenced by the presence of polymorphic variants. Given the loss of articular cartilage and with intention to restore damaged tissue, WISP-1 participates in the development of subchondral bone; further, its expression is highly increased in chondrocytes of OA patients. The aim of this study was to evaluate gene frequencies of HIF1A and WISP1 polymorphisms in Mexican patients suffering from knee OA.
  
  
  METHODS
  We determined HIF1A rs11549465 (P582S), rs11549467 (A588T), and rs2057482 (C191T), and WISP1 rs2929970 (A2364G) polymorphisms in 70 Mexican patients with knee OA and compare them to those present in 66 ethnically matched healthy controls. Genotyping for these polymorphisms was performed by Real-Time PCR using TaqMan probes.
  
  
  RESULTS
  Gene frequencies exhibited a significant increase of the CC genotype of rs11549465 polymorphism in knee OA patients as compared with those present in controls (P = 0.003 OR = 5.7, 95% CI = 1.7-21.6); CT genotype and T allele showed decreased frequency in the knee OA group vs. the controls (P = 0.003 OR = 0.2, CI = 0.05-0.6; and P = 0.004 OR = 0.2, CI = 0.05-0.65, respectively). Allele frequencies of the other polymorphic variants were similar in both patients and controls.
  
  
  CONCLUSIONS
  These results suggest that the presence of the rs11549465 SNP (HIF1A) plays a role protective in the loss of articular cartilage in our population, and offers the possibility to further study the molecular mechanisms within cartilage and subchondral bone.
authors: Synovioanalysis Molecular Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. javier_astrofan@hotmail.com.|Escuela Superior de Medicina, Instituto Politécnico Nacional, Calle Salvador Díaz Mirón esq. Plan de San Luis, Col. Santo Tomás, 11340, México, D.F., Mexico. javier_astrofan@hotmail.com.
authors: Javier
authors: J
authors: Fernández-Torres
authors: Musculoskeletal Ultrasound Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. cristy_hernandez@hotmail.com.
authors: Cristina
authors: C
authors: Hernández-Díaz
authors: Rheumatology Service, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. rolespi@yahoo.com.
authors: Rolando
authors: R
authors: Espinosa-Morales
authors: Cirugía Ortopédica, Centro Médico ABC, Av. Carlos Graef Fernández 154, Col. Tlaxala Santa Fe, Cuajimalpa, 05300, Mexico, D.F., Mexico. jvrcamacho@hotmail.com.
authors: Javier
authors: J
authors: Camacho-Galindo
authors: Departamento de Infectología e Inmunología Perinatal, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Secretaría de Salud, Calle Montes Urales 800, Col. Lomas Virreyes, Miguel Hidalgo, 11000, México, D.F., Mexico. ngalindosevilla@hotmail.com.
authors: Norma del Carmen
authors: Ndel C
authors: Galindo-Sevilla
authors: Synovioanalysis Molecular Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. lopez_macay@hotmail.com.
authors: Ámbar
authors: Á
authors: López-Macay
authors: Synovioanalysis Molecular Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. yesszamudio@gmail.com.|Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomás, Miguel Hidalgo, 11340, México, D.F., Mexico. yesszamudio@gmail.com.
authors: Yessica
authors: Y
authors: Zamudio-Cuevas
authors: Synovioanalysis Molecular Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. karinabiologist@hotmail.com.
authors: Karina
authors: K
authors: Martínez-Flores
authors: Synovioanalysis Molecular Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. mgso82@hotmail.com.
authors: Mónica Guadalupe
authors: MG
authors: Santamaría-Olmedo
authors: Musculoskeletal Ultrasound Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. carpineda@yahoo.com.
authors: Carlos
authors: C
authors: Pineda
authors: Immunogenetics Division, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ), Secretaría de Salud, Vasco de Quiroga 15, Col. Sección XVI, Tlalpan, 14000, Mexico, D.F., Mexico. julgrate@yahoo.com.
authors: Julio
authors: J
authors: Granados
authors: Synovioanalysis Molecular Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. ameria.justice@gmail.com.
authors: Gabriela Angélica
authors: GA
authors: Martínez-Nava
authors: Synovioanalysis Molecular Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. dr.gmarwin@gmail.com.
authors: Marwin
authors: M
authors: Gutiérrez
authors: Synovioanalysis Molecular Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra", Secretaría de Salud, Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico, D.F., Mexico. allorey@yahoo.com.
authors: Alberto G
authors: AG
authors: López-Reyes
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000502:physiology; D002356:Cartilage / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000502:physiology*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D016037:Single-Blind Method
chemical_list: D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011518:Proto-Oncogene Proteins