title: Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women.
abstract: OBJECTIVE
  Osteoporosis and obesity are complex diseases with a strong genetic component. Bone mineral density (BMD) and body mass index (BMI) linkage studies identified a locus at 1q21-23, where the interleukin-6 receptor (IL6R) gene is located. The IL6R and the gp130 receptors are the mediators of IL6 action. Serum levels of IL6 and sIL6R (the soluble form of IL6R) are higher in several diseases such as osteoporosis or obesity. Variants at IL6R have been associated with BMI and obesity. However, IL6R is an as-yet-unexplored osteoporosis candidate gene.
  
  
  METHODS
  In the present study we analysed two polymorphisms in the IL6R promoter, -1435 C/T (rs3887104) and -208 G/A (rs4845617), and the Asp358Ala polymorphism (rs8192284), in relation to both BMD and BMI in a cohort of 559 postmenopausal Spanish women.
  
  
  RESULTS
  The promoter polymorphisms, -1435 C/T and -208 G/A were associated with femoral neck (FN) BMD (P=0.011 and P=0.025 respectively). The C-A and T-G promoter haplotypes were also associated with FN BMD. Additionally, the Asp358Ala variant was associated with lumbar spine BMD (P=0.038). Finally, the -208 G/A polymorphism and the C-G and C-A haplotypes were associated with BMI and obesity, where GG was the risk genotype (P=0.033 for BMI; P=0.010 for obesity).
  
  
  CONCLUSIONS
  These data suggest that variants in the IL6R gene are not only involved in the determination of BMI but also relevant for the determination of BMD. The IL6R gene may belong to the growing list of genes known to be involved in both phenotypes.
authors.affiliation: Department of Genetics, University of Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Bustamante
authors.forename: X
authors.initials: X
authors.lastname: Nogués
authors.forename: L
authors.initials: L
authors.lastname: Mellibovsky
authors.forename: L
authors.initials: L
authors.lastname: Agueda
authors.forename: S
authors.initials: S
authors.lastname: Jurado
authors.forename: E
authors.initials: E
authors.lastname: Cáceres
authors.forename: J
authors.initials: J
authors.lastname: Blanch
authors.forename: R
authors.initials: R
authors.lastname: Carreras
authors.forename: A
authors.initials: A
authors.lastname: Díez-Pérez
authors.forename: D
authors.initials: D
authors.lastname: Grinberg
authors.forename: S
authors.initials: S
authors.lastname: Balcells
mesh_terms: D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D017698:Postmenopause / Q000235:genetics*; D011446:Prospective Studies; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D013030:Spain
chemical_list: D019947:Receptors, Interleukin-6