American Journal of Medical Genetics 119A:132–136 (2003) IL-1a (889) Promoter Polymorphism Is a Risk Factor for Osteomyelitis Vı ´ctor Asensi, 1 * Victoria Alvarez, 1 Eulalia Valle, 1 Alvaro Meana, 1 Joshua Fierer, 2 Eliecer Coto, 1 Jose ´ Antonio Carton, 1 Jose ´ Antonio Maradona, 1 Jose ´ Paz, 1 Maria Angeles Dieguez, 1 Bele ´n de la Fuente, 3 Alfonso Moreno, 1 Silvino Rubio, 4 Maria Jose ´ Tuya, 5 Julia ´ n Sarasu ´ a, 1 Sara Llames, 1 and Jose ´ Manuel Arribas 1 1 Infectious Diseases, Molecular Genetics, Traumatology and Plastic Surgery Departments, Hospital Central de Asturias, Oviedo University Medical School, Oviedo, Spain 2 Infectious Diseases Section, VAMC, University of California, San Diego, California 3 Hospital de Cabuen ˜ es, Gijo ´ n, Avile ´ s, Asturias, Spain 4 Hospital Carmen y Severo Ochoa, Cangas, Avile ´ s, Asturias, Spain 5 HospitalSan Agustı´n, Avile ´ s, Asturias, Spain As osteomyelitis (OM) induces the synth- esis of inflammatory cytokines and IL-1 mediates bone resorption by osteoclasts we determined if there is an association between certain common polymorphisms of the genes encoding proinflammatory cyto- kines (IL-1a and b, IL-6, TNF-a) and OM in adults. The IL-1a (889) TT genotype was significantly more frequent among 52 OM patients than in 109 healthy controls (13/52, [25.0%] vs. 9/109, [8.3%], P ¼ 0.0081, x 2 ¼ 7.01, OR ¼ 3.7, 95% CI, 1.35–10.34). Patients who were homozygous for the T allele were younger than the rest of the OM patients (mean age 35.7  11.5 vs. 58.1  18.6 years, P ¼ 0.001). IL-1b TT (þ3953) polymorphism was also more frequent in OM patients (P ¼ 0.014, x 2 ¼ 5.12, OR ¼ 5.1, 95% CI, 1.21– 52.14), but IL-1b is in linkage disequilibrium with the IL-1a *T (P < 0.001). Route of infec- tion, chronicity of the infection, type of microorganism isolated, and frequency of relapses were similar in patients with and without the IL-1a TT genotype. There were no associations between OM and polymorph- isms of other cytokines genes. IL-1a serum levels were significantly increased in all the OM patients independently of their IL-1 genotype compared to the controls (P ¼ 0.021). Although IL-1a serum levels were not significantly higher in patients with the IL-1a (889) polymorphism, this does not exclude a difference in production of IL-1a by osteoclasts or other inflammatory cells at the site of infection. ß 2003 Wiley-Liss, Inc. KEY WORDS: osteomyelitis; pathogenesis; cytokines; IL-1b (þ3953); IL- 1a (889) polymorphism INTRODUCTION Osteomyelitis (OM) is a difficult-to-treat infection characterized by progressive inflammatory destruction of the infected bone and new apposition of bone at the site of infection. In adults OM is usually a complication of open wounds involving the bone, either from frac- tures, surgery, or both. It is reported that 0.4 – 7% of open fractures and orthopedic operations are complicated by OM [Cierny and Mader, 1984; Roesgen et al., 1989; Lew and Waldvogel, 1997]. This infection can develop as well in a non-injured bone after bacteremia, mostly in prepubertal children and in elderly patients. In the latter the infection involves the axial skeleton, whereas the epiphyses of the long bones are most often the site of hematogenous OM in children. Staphylococcus aureus is the microorganism most frequently cause of both post- traumatic and hematogenous OM. In spite of appro- priate combined medical and surgical therapies up to 30% of OM become chronic causing major economic losses and personal morbidity and mortality [Lew and Waldvogel, 1997]. Much attention has been dedicated to improving the surgical and medical treatment of OM but little progress has been made toward understanding its pathogenesis. It is clear that the risk of OM is main- ly influenced by local factors related to the nature and severity of the underlying bone injury and the Grant sponsor: Oviedo University (to Dr. Victor Asensi); Grant number: IR-00-519-59. *Correspondence to: Dr. Vı ´ctor Asensi, Infectious Diseases Unit, Hospital Central de Asturias, Oviedo University Medical School, c/Celestino Villamil s/n, 33006 Oviedo, Spain. E-mail: vasensia@medynet.com Received 5 April 2002; Accepted 7 October 2002 DOI 10.1002/ajmg.a.20137 ß 2003 Wiley-Liss, Inc.