title: Combined effects of CXCL8 and CXCR2 gene polymorphisms on susceptibility to systemic sclerosis.
abstract: A previous study suggested that the CXCR2 (+1208) TT genotype was associated with increased risk of systemic sclerosis (SSc). In the present study, we investigated the influence of variation in the CXCL8 and CXCR2 genes on susceptibility to SSc and combined the variant alleles of these genes to analyze their effects on SSc.
  
  
  METHODS
  One fifty one patients with SSc and 147 healthy bone marrow donors were enrolled in a case-control study. Blood was collected for DNA extraction; typing of CXCL8 (-251) T/A and CXCR2 (+1208) T/C genes was made by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by agarose gel electrophoresis.
  
  
  RESULTS
  The CXCR2-TC genotype was significantly less frequent in patients (23.8% versus 55.1% in controls; P<0.001, OR=0.26, 95%CI=0.15-0.43), whereas the CXCR2-CC genotype was significantly more frequent (44.4% versus 22.4% in controls; P<0.001, OR=2.76, 95%CI, 1.62-4.72). When CXCR2 and CXCL8 combinations were analyzed, the presence of CXCR2 T in the absence of CXCL8 A (CXCR2 T+/CXCL8 A-) was more frequent in patients than in controls (34.5% versus 3.5%; P<0.001, OR=14.50, 95%CI=5.04-41.40). However, CXCR2 TT and CXCL8 A were significantly more common in controls (100%) than in patients (58.3%) (P<0.001). Likewise, the presence of CXCR2 TC and CXCL8 A was more frequent in controls (95.1%) than in patients (75%) (P=0.004). Furthermore, the CXCR2-CC genotype in CXCL8 A was more frequent in patients (59.7% versus 0% in controls; P<0.001, adjusted OR=98.67, 95%CI=6.04-1610.8). In patients, a high frequency was observed in combination with the CXCL8 TA and AA genotypes (P<0.001; OR=28.92), whereas in controls, there was a high frequency of combination with CXCL8 T (P<0.001; OR=0.03) and TT (P<0.001; OR=0.01).
  
  
  CONCLUSIONS
  These findings suggest a protective role of CXCL8 (-251) A in the CXCR2 (+1208) TT and TC genotypes and an increased risk of CXCL8 (-251) A in association with the CXCR2 (+1208) CC genotype in SSc patients.
authors: Graduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul. Porto Alegre, RS, Brazil. patysalim@gmail.com
authors: Patricia Hartstein
authors: PH
authors: Salim
authors: Mariana
authors: M
authors: Jobim
authors: Markus
authors: M
authors: Bredemeier
authors: José Arthur Bogo
authors: JA
authors: Chies
authors: João Carlos Tavares
authors: JC
authors: Brenol
authors: Luiz Fernando
authors: LF
authors: Jobim
authors: Ricardo Machado
authors: RM
authors: Xavier
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000235:genetics*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B