title: Association between rs267196 and rs267201 of BMP6 gene and osteonecrosis among sickle cell aneamia patients.
abstract: OBJECTIVE
  The skeletal manifestations of sickle cell disease are the result of changes in bone and bone marrow caused by chronic tissue hypoxia that is exacerbated by episodic occlusion of the microcirculation by the abnormal sickle cells. Furthermore, the occurrence of osteonecrosis is under the control of some modifier gene. BMP6 (Bone morphogenetic protein) has been reported as associated with osteonecrosis in sickle cell anemia (SCA). Herein, we intend to study the impact of rs267196, rs267201, rs408505 and rs449853 of BMP6 gene in the occurrence of osteonecrosis among sickle cell patients in Tunisia.
  
  
  METHODS
  Our study involved 100 SCA patients among whom 19 have osteonecrosis of the head of the femur. The latter polymorphisms of BMP6 gene were analyzed for all subjects by PCR/sequencing. To test for trait association with the candidate SNPs, genotype and allele frequencies between cases (osteonecrosis group) and controls (non-osteonecrosis group) were compared using Pearson's chi_square test with a significance threshold of P<0.05 (compare 2, version 1.02).
  
  
  RESULTS
  Our findings showed that the patients carried genotype TA of rs 267196 and genotype AG of rs267201 present a high risk factor for developing osteonecrosis RR=1.317 and RR=1.3 respectively. The results showed a significant association between the alleles A of rs 267196 and G of rs267201 and osteonecrosis P=0.0023; RR=2.42 and P=0.041; RR=2.24 respectively. Interestingly, SCA patients with the combined genotype TA/AG were found to be at higher risk of developing osteonecrosis (P=0.009). As for rs408505 and rs449853 of BMP6 gene no significant association was found among SCA patients.
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Tunis El Manar University, Pasteur Institute of Tunis, Tunis, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Chaouch
authors.forename: Miniar
authors.initials: M
authors.lastname: Kalai
authors.forename: Manel Ben
authors.initials: MB
authors.lastname: Jbara
authors.forename: Arij Ben
authors.initials: AB
authors.lastname: Chaabene
authors.forename: Imen
authors.initials: I
authors.lastname: Darragi
authors.forename: Dorra
authors.initials: D
authors.lastname: Chaouachi
authors.forename: Fethi
authors.initials: F
authors.lastname: Mallouli
authors.forename: Raouf
authors.initials: R
authors.lastname: Hafsia
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Ghanem
authors.forename: Salem
authors.initials: S
authors.lastname: Abbes
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010020:Osteonecrosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012334:RNA, Neoplasm / Q000235:genetics*; D012307:Risk Factors
chemical_list: C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6; D012334:RNA, Neoplasm