title: Interleukin-1 receptor antagonist gene polymorphisms are associated with disease severity in Black South Africans with rheumatoid arthritis.
abstract: OBJECTIVE
  To test for genetic associations between polymorphisms of the interleukin-1 (IL-1) gene cluster and disease susceptibility and severity in Black South Africans with rheumatoid arthritis (RA).
  
  
  METHODS
  Allele and genotype frequencies of IL1B (-511) and (+3954) and IL1RN variable number of tandem repeat (VNTR) and (+2018) were compared between 141 RA patients and 101 healthy controls.
  
  
  RESULTS
  No significant differences in allelic distribution at the four loci were observed between RA patients and controls. Within the RA group, the IL1RN*2 (two repeats of an 86bp tandem repeat) at the IL1RN VNTR locus was independently associated with higher Larsen radiologic damage scores (LDS), corrected for disease duration (p=0.04). Moreover, the inferred haplotype, consisting of IL1RN*2 and (+2018) 'C' allele, was associated with significantly higher LDS, on average 15 points higher, compared to the base haplotype of IL1RN*long (three or more repeats) and (+2018) 'T' allele (p=0.009). The common IL1B (-511) 'T' allele was associated with a poorer modified health assessment questionnaire disability index (p=0.02).
  
  
  CONCLUSIONS
  Our findings provide further evidence of a possible role of polymorphisms of the IL-1 gene cluster in disease severity in RA, and particularly IL1RN*2 as a marker of erosive joint damage in Black South Africans with RA.
authors.affiliation: Division of Human Genetics, National Health Laboratory Service, Cnr Hospital and de Korte streets, Braamfontein, PO Box 1038, Johannesburg 2000, South Africa.
authors.forename: Steven
authors.initials: S
authors.lastname: Lubbe
authors.forename: Mohammed
authors.initials: M
authors.lastname: Tikly
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Bridget
authors.initials: B
authors.lastname: Hodkinson
authors.forename: Michele
authors.initials: M
authors.lastname: Ramsay
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000208:ethnology* / Q000235:genetics*; D044383:Black People; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta; D008297:Male; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D013019:South Africa / Q000453:epidemiology; D020080:Tandem Repeat Sequences
chemical_list: C508585:IL1B protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta