title: Association of interleukin-6 gene polymorphisms with hand osteoarthritis and hand osteoporosis.
abstract: OBJECTIVE
  Several genes, including IL-6 encoding pro-inflammatory cytokines, are involved in development of osteoarthritis and osteoporosis. The association of radiographic hand osteoarthritis (RHOA) and osteoporosis related phenotypes (RHOP) with polymorphisms in IL-6 has been reported inconsistently. The aim of this study was to examine the association, between RHOA and RHOP and IL-6 polymorphisms in two independent samples.
  
  
  METHODS
  Two samples: UK females, including 1440 individuals assessed for RHOA and 3470 assessed for RHOP; Chuvash pedigree including 1499 females and males were assessed for RHOP and RHOA. SNPs were genotyped in the IL-6 genomic region, and used in association analysis with RHOA and RHOP phenotypes.
  
  
  RESULTS
  RHOP phenotypes showed similar heritability estimates in both samples, ranging from 34.5 ± 5.5% to 61.0 ± 2.4%. RHOA in Chuvash had substantially lower heritability estimates compared to twins (e.g. OSP scores: 11.8 ± 2.3% vs. 39.2 ± 4.1%) with much higher prevalence and considerably stronger correlation with age (r = 0.811 vs. r = 0.505). RHOA in Chuvash sample may be traumatic in nature, caused by heavy and prolonged manual work related to their private farming. There were a number of statistically significant association results with both types of phenotypes. The most consistent result was obtained for JSN in both samples with SNP from the same haploblock. Their combined probability of no association was only p = 0.000003. Additionally, there were SNPs common for both RHOA and RHOP.
  
  
  CONCLUSIONS
  We have shown polymorphisms in IL_6 are significantly associated with RHOA and hand RHOP in two samples having different ethnicity and lifestyle. Age × environment × genes interaction appears as an important factor of RHOA manifestation and progression.
authors.affiliation: Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Blumenfeld
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London St Thomas' Hospital Campus, London, UK.
authors.forename: Frances M K
authors.initials: FM
authors.lastname: Williams
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London St Thomas' Hospital Campus, London, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Valdes
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London St Thomas' Hospital Campus, London, UK.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Hart
authors.affiliation: Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ida
authors.initials: I
authors.lastname: Malkin
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London St Thomas' Hospital Campus, London, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Twin Research and Genetic Epidemiology, King's College London St Thomas' Hospital Campus, London, UK. Electronic address: gregl@post.tau.ac.il.
authors.forename: Gregory
authors.initials: G
authors.lastname: Livshits
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006225:Hand / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000276:immunology; D010024:Osteoporosis / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D014427:Twins / Q000235:genetics; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6
keywords: BMD; Joint space narrowing; Kellgren/Lawrence; Osteophytes; SNP