title: Single nucleotide polymorphisms other than factor V Leiden are associated with coagulopathy and osteonecrosis of the femoral head in Chinese patients.
abstract: Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (87.6%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.62; 95% confidence interval: 1.44-14.8) of having coagulation abnormalities than did those without the mutation (wild-type) (χ(2) p  =  0.006). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head.
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Kou-Ti
authors.initials: KT
authors.lastname: Peng
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Kuo-Chin
authors.initials: KC
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Tsan-Wen
authors.initials: TW
authors.lastname: Huang
authors.affiliation: Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taiwan.
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Wei-Hsiu
authors.initials: WH
authors.lastname: Hsu
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Robert W W
authors.initials: RW
authors.lastname: Hsu
authors.affiliation: Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
authors.forename: Steve W N
authors.initials: SW
authors.lastname: Ueng
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Mel S
authors.initials: MS
authors.lastname: Lee
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D001778:Blood Coagulation Disorders / Q000235:genetics*; D005165:Factor V / Q000235:genetics*; D005271:Femur Head Necrosis / Q000235:genetics*; D005340:Fibrinogen / Q000378:metabolism; D005787:Gene Frequency; D006801:Humans; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D005165:Factor V; D005340:Fibrinogen