| 1. |
- Rueda, B., et al.
(författare)
-
The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype
- 2009
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:11, s. 2071-2077
-
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.
|
|
| 2. |
- Rueda, B., et al.
(författare)
-
A large multicentre analysis of CTGF - 2945 promoter polymorphism does not confirm association with systemic sclerosis susceptibility or phenotype
- 2009
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:10, s. 1618-1620
-
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.
|
|
| 3. |
|
|
| 4. |
- Watson, L, et al.
(författare)
-
Predictors of lung function and its decline in mild to moderate COPD in association with gender: Results from the Euroscop study
- 2006
-
Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 100:4, s. 746-753
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is increasing appreciation of gender differences in COPD but scant data whether risk factors for tow lung function differ in men and women. We analysed data from 3 years follow-up in 178 women and 464 men with COPD, participants in the Euroscop Study who were smokers unexposed to inhaled corticosteroids. Methods: Explanatory variables of gender, age, starting age and pack-years smoking, respiratory symptoms, FEV1%FVC and FEV1%IVC (clinically important measures of airway obstruction), body mass index (BMI), and change in smoking were included in multiple linear regression models with baseline and change in postbronchodilator FEV1 as dependent variables. Results: Reduced baseline FEV1 was associated with respiratory symptoms in men only. Annual decline in FEV1 was not associated with respiratory symptoms in either men or women, and was 55 ml less in obese men (BMI >= 30 kg/m(2)) than men having normal BMI, an effect not seen in women. It was 32ml faster in women with FEV1%FVC < median than women with less airway obstruction, a larger difference than in men (8ml per year). It was 17.7ml/year faster when increasing the daily number of cigarettes by 10 in men only, but not significantly greater than in women. Conclusion: Respiratory symptoms were associated with reduced baseline FEV, in men with COPD. In men, obesity was associated with reduced decline and increasing the number of cigarettes smoked with increased decline in lung function. In women more severe airway obstruction was associated with accelerated decline.
|
|
| 5. |
- He, T., et al.
(författare)
-
The role of colonic metabolism in lactose intolerance
- 2008
-
Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 38:8, s. 541-547
-
Forskningsöversikt (refereegranskat)abstract
- Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.
|
|
