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- Rueda, B., et al.
(författare)
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The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype
- 2009
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:11, s. 2071-2077
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P < 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype.
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| 2. |
- Rueda, B., et al.
(författare)
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A large multicentre analysis of CTGF - 2945 promoter polymorphism does not confirm association with systemic sclerosis susceptibility or phenotype
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:10, s. 1618-1620
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To conduct a replication study to investigate whether the 2945 CTGF genetic variant is associated with systemic sclerosis (SSc) susceptibility or specific SSc phenotype. Methods: The study population comprised 1180 patients with SSc and 1784 healthy controls from seven independent case-control sets of European ancestry (Spanish, French, Dutch, German, British, Swedish and North American). The 2945 CTGF genetic variant was genotyped using a Taqman 59 allelic discrimination assay. Results: An independent association study showed in all the case-control cohorts no association of the CTGF 2945 polymorphism with SSc susceptibility. These findings were confirmed by a meta-analysis giving a pooled OR=1.12 (95% CI 0.99 to 1.25), p=0.06. Investigation of the possible contribution of the 2945 CTGF genetic variant to SSc phenotype showed that stratification according to SSc subtypes (limited or diffuse), selective autoantibodies (anti-topoisomerase I or anticentromere) or pulmonary involvement reached no statistically significant skewing. Conclusion: The results do not confirm previous findings and suggest that the CTGF 2945 promoter polymorphism does not play a major role in SSc susceptibility or clinical phenotype.
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