title: Effect of RAGE polymorphisms on susceptibility to and severity of osteoarthritis in a Han Chinese population: a case-control study.
abstract: Recent studies have revealed that the inflammatory process plays a role in the pathogenesis of osteoarthritis (OA). The S100 family and receptor for advanced glycation end products (RAGE) participate in regulating inflammation, even in the production of matrix metalloproteinases (MMPs). MMP-1 degrades cartilage, which may result in OA development. Moreover, polymorphisms in RAGE, S100A8, and MMP-1 have a marked effect on ligand binding and transcription regulating. In this study, we investigated the potential genetic contribution of the RAGE, S100A8, and MMP-1 genes to OA. We performed a matched case-control association study and genotyped OA patients and healthy controls, who were analyzed by polymerase chain reaction-restriction fragment length polymorphism assays. A total of 207 patients were diagnosed with knee OA and underwent total knee replacement. The control group included 207 individuals who had standard X-rays of the knee joints to confirm K/L < 2 and were matched by age and gender. Single-nucleotide polymorphisms in RAGE (-429T/C, -374T/A, and 557G/A), S100A8 (rs3795391A/G), and MMP-1 (-1607 1G/2G, -755G/T, and -519A/G) were evaluated. RAGE -374T/A, S100A8 rs3795391A/G, MMP-1 -1607 1G/2G, -755G/T, and -519A/G showed no significant difference between OA patients and healthy controls. RAGE -429T/C and 557G/A showed a significant association between OA patients and healthy controls (P = 0.016 and 0.047, respectively). In haplotype analyses, no RAGE and MMP-1 haplotypes showed associations with OA. Our results suggest that the investigated polymorphism in the RAGE gene play a role in OA in the Han Chinese population.
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, China.
authors.forename: S Y
authors.initials: SY
authors.lastname: Chuang
authors.affiliation: Department of Family and Community Medicine, Tri-Service General Hospital, Taipei, Taiwan, China.
authors.forename: W H
authors.initials: WH
authors.lastname: Fang
authors.affiliation: Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan, China.
authors.forename: G S
authors.initials: GS
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, China.
authors.forename: C C
authors.initials: CC
authors.lastname: Wang
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, China.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Department of Aviation Medicine and Physical Examination, National Defense Medical Center Tri-Service General Hospital Songshan Branch, Taipei, Taiwan, China.
authors.forename: M Y
authors.initials: MY
authors.lastname: Chu
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, China.
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan, China.
authors.forename: W
authors.initials: W
authors.lastname: Su
authors.affiliation: Division of Radiology, National Defense Medical Center Tri-Service General Hospital Songshan Branch, Taipei, Taiwan, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Chen
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, China.
authors.forename: Y T
authors.initials: YT
authors.lastname: Yang
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, China.
authors.forename: S L
authors.initials: SL
authors.lastname: Su
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D040501:Calgranulin A / Q000235:genetics; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020370:Osteoarthritis, Knee / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D040501:Calgranulin A; D000067759:Receptor for Advanced Glycation End Products; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1