title: Interleukin-1α gene variants influence bone mineral density and the risk of osteoporotic hip fractures in elderly Slovenian people.
abstract: BACKGROUND
  Osteoporosis is a skeletal disorder, characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to increased risk of fracture. Recently, the role of age-related pro-inflammatory cytokines, such as interleukin (IL)-1α, in stimulating bone resorption has been suggested. As osteoporosis has a strong genetic background, the aim of our study was to evaluate the association of two IL-1α gene single nucleotide polymorphisms (SNPs) rs2071375 (+12534G>A) and rs17651 (+4845G>T) with osteoporotic phenotypes as well as to find the association with IL-1α gene expression in human bone tissue.
  
  
  METHODS
  Genotyping was performed in 671 Slovenian participants, 125 elderly men, 490 post- and 56 premenopausal women. Bone mineral density (BMD) at the lumbar spine, femoral neck and total hip were measured. Biochemical markers of bone turnover were measured in women.
  
  
  RESULTS
  Significant association of GG/TA haplotype with higher femoral neck and total hip BMD in elderly men and women was shown (p=0.009 and 0.030, respectively). In men, the association of the GG/GG haplotype with higher femoral neck BMD was of limited statistical significance (p=0.050). In women, significant association of studied genetic variants with serum C-terminal crosslinking telopeptides of type I collagen and bone alkaline phosphatase were found (p=0.033 and 0.029, respectively). No influence on IL-1α expression was found. Finally, significantly lower odds ratio for hip fracture associated with the presence of TA haplotype was found (p=0.026).
  
  
  CONCLUSIONS
  Our results of the association of IL-1α gene single nucleotide polymorphisms (SNPs) rs2071375 (+12534G>A) and rs17651 (+4845G>T) with osteoporotic features indicate its role in pathogenesis of osteoporosis. However, these findings need further functional and clinical confirmation.
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia. janja.zupan@ffa.uni-lj.si
authors.forename: Janja
authors.initials: J
authors.lastname: Zupan
authors.forename: Nuša
authors.initials: N
authors.lastname: Pristovšek
authors.forename: Simona
authors.initials: S
authors.lastname: Mencej-Bedrač
authors.forename: Radko
authors.initials: R
authors.lastname: Komadina
authors.forename: Janez
authors.initials: J
authors.lastname: Preželj
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006620:Hip Fractures / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D058866:Osteoporotic Fractures / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017524:Slovenia
chemical_list: D015415:Biomarkers; D053582:Interleukin-1alpha