THU0078 Polymorphisms of the genes encoding CD40 and growth differentiation factor 15 and in the 9P21.3 region in patients with rheumatoid arthritis and cardiovascular disease

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 179.1-179
Author(s):  
S. Rantapää Dahlqvist ◽  
L. Ärlestig
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Genes Encoding

scholarly journals Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort

2017 ◽  
Vol 7 (2) ◽  
pp. 158-168 ◽  
Author(s):  
Amy S. You ◽  
Kamyar Kalantar-Zadeh ◽  
Lorena Lerner ◽  
Tracy Nakata ◽  
Nancy Lopez ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Mortality Risk ◽  
Hemodialysis Patients ◽  
Case Mix ◽  
Dialysis Patients ◽  
Protein Energy Wasting ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Protein Energy ◽  
Dialysis Vintage

Background/Aims: Cardiovascular disease and protein-energy wasting are among the strongest predictors of the high mortality of dialysis patients. In the general population, the novel cardiovascular and wasting biomarker, growth differentiation factor 15 (GDF15), is associated with decreased survival. However, little is known about GDF15 in dialysis patients. Methods: Among prevalent hemodialysis patients participating in a prospective study (October 2011 to August 2015), we examined the association of baseline GDF15 levels with all-cause mortality using unadjusted and case mix-adjusted death hazard ratios (HRs) that controlled for age, sex, race, ethnicity, diabetes, and dialysis vintage. Results: The mean age ± SD of the 203 patients included in the study was 53.2 ± 14.5 years, and the cohort included 41% females, 34% African-Americans, and 48% Hispanics. GDF15 levels (mean ± SD 5.94 ± 3.90 ng/mL; range 1.58-39.8 ng/mL) were higher among older patients and were inversely associated with serum creatinine concentrations as a surrogate for muscle mass. Each 1.0 ng/mL increase in GDF15 was associated with an approximately 17-18% higher mortality risk in the unadjusted and case mix models (p < 0.05). Increments of about 1 SD (a 4.0 ng/mL increase in GDF15) were associated with a nearly 2-fold higher death risk. The highest GDF15 tertile was associated with higher mortality risk (reference: lowest tertile): the HRs (95% CI) were 3.19 (1.35-7.55) and 2.45 (1.00-6.00) in the unadjusted and the case mix-adjusted model, respectively. These incremental death trends were confirmed in cubic spline models. Conclusion: Higher circulating GDF15 levels are associated with higher mortality risk in hemodialysis patients. Future studies are needed to determine whether GDF15 may represent a novel therapeutic target for cardiovascular disease, wasting, and death in this population.

scholarly journals The impact of growth differentiation factor 15 on the risk of cardiovascular disease: evidence from Mendelian randomization study

2020 ◽  
Author(s):  
Zhuo Wang ◽  
Fangkun Yang ◽  
Menghuai Ma ◽  
Qinyi Bao ◽  
Jinlian Shen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Causal Relationship ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Cardioembolic Stroke ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Increased Risk ◽  
The Impact

Abstract Background: Growth differentiation factor 15(GDF-15) concentration is apparently associated with cardiovascular disease, but whether there is a causal relationship has not been testified. Methods: We utilized Mendelian randomization to assess the function of GDF-15 in incidence of cardiovascular disease. The single-nucleotide polymorphism- GDF-15 association evaluations came from meta-analysis of genome-wide association study (GWAS). Besides inverse-variance weighted, MR-Egger test and weighted median method were applied to examine sensitivity. Results: Base on the instruments, GDF-15 level linked to increased risk of cardioembolic stroke (1.06, OR 1.09 per SD increase, 95% CI 1.01, 1.19) and atrial fibrillation (OR 1.03 per SD increase, 95% CI 1.0, 1.06). However, the significant causal relationship between GDF-15 and the other cardiovascular diseases was not found in our work. Conclusions: The result suggested that GDF-15 is causally associated with the risk of cardioembolic stroke and atrial fibrillation, providing conceivable strategies to alleviate the burden of cardiovascular disease.

scholarly journals Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

2012 ◽  
Vol 39 (5) ◽  
pp. 939-945 ◽  
Author(s):  
LISBETH ÄRLESTIG ◽  
SOLBRITT RANTAPÄÄ-DAHLQVIST
Keyword(s):  
Rheumatoid Arthritis ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Growth Differentiation Factor 15 ◽  
Vein Thrombosis ◽  
American College Of Rheumatology ◽  
Differentiation Factor ◽  
Chi Squared ◽  
Artery Disease ◽  
Ischemic Attack

Objective.Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM).Methods.A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 ± 13.2 years, and mean disease duration of 15.5 ± 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587),CD40(rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex).Results.The distribution of genotypes ofGDF15/MIC-1differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of theGDF15/MIC-1G allele (OR 2.21, 95% CI 1.17–4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15–3.19). Stroke/TIA in women was associated withGDF15/MIC-1GG genotype (OR 3.75, 95% CI 1.06–13.33), while stroke/TIA in men was associated withCD40homozygous major alleles (OR 6.48, 95% CI 1.31–32.0 and OR 2.78, 95% CI 0.78–9.91, respectively). DVT/PE was associated with polymorphism in theGDF15/MIC-1gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30–9.58).Conclusion.The gene polymorphisms analyzed were associated with different ATM in RA. TheGDF15/MIC-1gene polymorphism was also associated with RAper se, suggesting a common etiology for RA and ATM.

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