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CART predictive model: the main predictive factors significantly associated with the development of CVD in RA are clinical and sociodemographic cluster, mean arterial pressure (MAP), and current smoking, with variable importance scores higher than 0.73.
Source publication
Rheumatoid arthritis (RA) is the most common autoimmune arthropathy worldwide. The increased prevalence of cardiovascular disease (CVD) in RA is not fully explained by classic risk factors. The aim of this study was to determine the influence of rs1058587 SNP within GDF15(MIC1) gene on the risk of CVD in a Colombian RA population. Methods. This was...
Citations
... On contrary, the CC-genotype was associated with elevated low density lipoprotein cholesterol (LDLc) and total cholesterol (TC) in individuals with plaques 73 . Farias et al. found no association between two polymorphisms (-607C/A and -137G/C) of the IL-18 gene and RA nor risk factors for CVD; similarly no influence was found of the rs1058587 SNP within GDF15 (MIC1) gene on the development of CVD 74,75 . Although discrepant with a previous report 76 , Agca et al. examined the effects of the Interferon regulatory factor 5 (IRF5) gene polymorphisms (rs2004640 and rs4728142) and found that some genotypes were associated with cIMT and cIMT progression, but not CV events in RA patients, implicating a role of the IRF5 transcription pathway in atherosclerosis 77 . ...
We aimed to explore whether the rs2073618 variant (G1181C) of the osteoprotegerin (OPG) gene and the methylenetetrahydrofolate reductase (MTHFR) rs1801131 (A1298AC) and rs1801133 (C677T) gene polymorphisms contribute to rheumatoid arthritis (RA) susceptibility and RA related subclinical atherosclerosis. Overall 283 RA patients and 595 healthy controls (HC) were genotyped for common variants of the OPG and MTHFR genes using PCR based assays. Clinical and laboratory parameters were recorded following thorough chart review. Surrogate markers of subclinical atherosclerosis (Carotid/Femoral intima media thickness/plaque formation) along with traditional risk factors for atherosclerosis were assessed in all RA patients and 280HC. Increased prevalence of the CC genotype of the rs2073618 variant was detected in RA patients vs HC (42.4% vs. 33%, p-value: 0.04). RA patients with high serum titers of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibodies displayed increased prevalence of the CC genotype of the rs2073618 variant of the OPG gene compared to HC (48.6% and 47.5 vs 33.3%, p-values: 0.0029and 0.0077 respectively). Of interest, this genotype turned to be associated with higher carotid IMT scores (0.872 ± 0.264 vs 0.816 ± 0.284, p-value: 0.01) and marginally with higher rates of carotid plaque formation (66% vs 54.1%, p = 0.06). The MTHFR 1298CC genotype was more prevalent only in the anti-CCP positive group compared to HC, with no associations detected with markers of subclinical atherosclerosis, following adjustment for traditional cardiovascular (CVD) risk factors. Reduced rates of carotid/femoral plaque formation were detected among RA patients harboring the MTHFR TT genotype (52.4 vs 72.7, p-value: 0.009, respectively). This association remained significant following adjustment for classical CVD risk factors (OR [95% CI 0.364 [0.173–0.765], p-value: 0.008). Genetic variations of the osteoprotegerin and MTHFR genes seem to increase susceptibility for seropositive RA and potentially contribute to subclinical atherosclerosis linked to RA. Larger studies are needed to confirm these findings.
... The wild-type variant (H) is associated with HG in this study, and has been associated with increased serum GDF15, and with a reduction in body weight, abdominal fat, body mass index and obesity. 16,33 Cryo-EM predicted H6D is an interface residue that may partially alter GDF15-GFRAL interaction. ...
Objective: A genome-wide association study (GWAS) linked the placenta and appetite hormone gene GDF15 to hyperemesis gravidarum (HG). The paradigm-changing finding shifted the field away from the prevailing hypotheses, but more evidence is needed. This study was performed to identify coding variants in addition to the non-coding variants implicated by GWAS.
Design: Case-control study.
Setting: Hyperemesis Gravidarum cases requiring intravenous fluid treatment for disease (n=926) and controls with normal or no nausea and vomiting of pregnancy (n=660) from the United States.
Methods: Whole exome-wide sequencing and genome informatics were performed using the standard Regeneron pipeline. All variants were compared between cases and controls using Dominant, Recessive, and Allelic models to identify variants with exome-wide significant p-values (p<10⁻⁰⁶ ). Odds ratios and associated p-values were calculated for exome-wide significant allele(s) in subgroups of genetically predicted ancestries. Variants were filtered to identify rare pathogenic variants occurring in >10 cases and no controls.
Main outcome measures: Identification of exome-wide significant and rare genetic variant(s) associated with HG.
Results: A common coding variant in GDF15 was the only exome-wide significant association, and a rare coding variant in GDF15 was the only predicted disease-causing variant occurring in 10 or more cases.
Conclusions: This study confirms the GWAS finding that GDF15 is the greatest genetic risk factor for HG. The new variants identified may have implications for prediction and diagnosis. The findings provide insight into the cause and molecular mechanisms for developing therapeutics for HG.
... They found that significant differences concerning rs1058587 polymorphism were not obtained between RA patients and controls. 20 Our findings were partly similar to the above findings. For example, regarding rs4808793, our results also showed no significant differences between RA patients and controls. ...
Purpose:
Rheumatoid arthritis (RA) is an inflammatory rheumatic disease, which has been demonstrated to correlate with mutated genetics. Growth and differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily and is expressed in different organs, tissues and immune cells. To date, limited studies have evaluated plasma levels of GDF-15 in RA patients, and whether GDF-15 gene polymorphisms correlate with RA risk in the Chinese Han population has not been clarified.
Patients and methods:
This case-control study recruited 910 age- and sex-matched RA patients and healthy controls. Plasma levels of GDF-15 were examined by enzyme linked immunosorbent assay, and polymorphisms (rs1055150, rs1058587, rs3787023, and rs4808793) were genotyped by KASP method.
Results:
RA patients had higher levels of GDF-15 as compared to that in healthy controls. Patients with positive CRP also showed higher levels of GDF-15 when compared to that in patients with negative CRP. Levels of GDF-15 correlated with disease activity score. Frequencies of GG, GC, GG+GC genotypes and G allele in GDF-15 gene rs1058587 were significantly elevated in RA patients compared to controls. Frequencies of CC genotype and C allele in GDF-15 gene rs3787023 were higher in RA patients compared to controls. Other polymorphisms did not correlate with RA susceptibility. Moreover, the four polymorphisms were not correlated with levels of GDF-15.
Conclusion:
Plasma levels of GDF-15 were elevated in RA patients and GDF-15 gene polymorphisms were related to RA risk in the Chinese Han population.
... On contrary, the CC-genotype was associated with elevated low density lipoprotein cholesterol (LDLc) and total cholesterol (TC) in individuals with plaques [70]. Farias et al. found no association between two polymorphisms (-607C/A and -137G/C) of the IL-18 gene and RA nor risk factors for CVD; similarly no in uence was found of the rs1058587 SNP within GDF15(MIC1) gene on the development of CVD [71,72]. Although discrepant with a previous report [73], Agca et al. examined the effects of the Interferon regulatory factor 5 (IRF5) gene polymorphisms (rs2004640 and rs4728142) and found that some genotypes were associated with cIMT and cIMT progression, but not CV events in RA patients, implicating a role of the IRF5 transcription pathway in atherosclerosis [74]. ...
Objective: To explore whether the osteoprotegerin (OPG) rs2073618 gene variant and the methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133 polymorphisms contribute to rheumatoid arthritis (RA) susceptibility and RA related subclinical atherosclerosis.
Methods: 283 RA patients and 595 healthy controls (HC) were genotyped for OPG and MTHFR gene variants using PCR based assays. Clinical, laboratory parameters and markers of subclinical atherosclerosis (Carotid/Femoral intima media thickness/plaque formation) along with traditional risk factors for atherosclerosis were assessed in RA patients and 280HC.
Results: Increased prevalence of the rs2073618CC genotype was detected in RA patients vs HC (p=0.04), especially in RA patients with high serum titers of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibodies compared to HC (p-values:0.0029 and 0.0077, respectively). This genotype was also associated with higher carotid-IMT scores (p=0.01) and marginally with higher rates of carotid plaque formation (p=0.06). MTHFR 1298CC genotype was more prevalent in the anti-CCP positive group compared to HC, with no associations detected with markers of subclinical atherosclerosis. Reduced rates of carotid/femoral plaque formation were detected among RA patients harboring the MTHFR 677TT genotype (p=0.009).
Conclusion: OPG and MTHFR gene variations seem to increase susceptibility for seropositive RA and potentially contribute to subclinical atherosclerosis linked to RA.
... Furthermore GDF-15 impacts the digestion system for carbohydrates What's more lipids. It assumes various parts done Different pathologies for example, such that cardiovascular disease, obesity, inflammation, Also growth because of its mitigating and antiproliferative properties [7]. ...
... Comparable with our comes about [10], [7], [3], [2] inferred that serum levels about gdf15were essentially higher in RA patients' assembly contrasted with solid controls and their investigations were Additionally once early RA ailment (duration under 12 months). ...
... В поперечном исследовании, в котором принял участие 681 пациент (498 женщин и 183 мужчины) с РА, был выявлен полиморфизм гена G F-15 / моноцит ингибирующего цитокина-1 с различными атеротромботическими событиями при РА (относительный риск (ОР) 2,21, 95 % доверительный интервал (ДИ) 1,17-4,18) [28]. Однако в более поздней работе, проведенной на 310 больных латиноамериканской популяции, страдающих РА и 228 пациентах (группа контроля) существенных различий в полиморфизме гена G F-15 обнаружено не было [29]. ...
This review presents relevant information about development and course of chronic heart failure (CHF) associated with rheumatoid arthritis (RA). One of the most discussed issues is the effect of systemic inflammatory process on prognosis of CHF. The review focused on current evidence for significance of this comorbidity in CHF. The diagnostic role of current immune markers, such as ga-lectin 3, pentraxin 3, growth differentiation factor 15, and osteopontin was described. The review discussed the significance of anti-inflammatory therapy for prognosis of CHF in the presence of systemic diseases. Possible beneficial effects of the basis therapy for RA on CHF outcomes were assessed. The authors noted a positive prognostic significance of methotrexate for the risk of decompen-sated CHF. © 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved.
... Genetic studies are useful for determining predictive factors for diagnosing patients, and numerous studies regarding the genetics of RA have been performed (6)(7)(8). It is assumed that genetic factors account for 60% of the cause of RA susceptibility. ...
Rheumatoid arthritis (RA) is a complex genetic disease. The lectin, galactoside-binding, soluble, 3 (LGALS3) gene, encodes a member of the galectin family of carbohydrate binding proteins, and is one of the best examples of a non-human leukocyte antigen gene associated with a risk for RA in various populations. In the current study, the association between LGALS3 rs4652 gene polymorphism and RA was examined. This case-control study was performed on the 120 patients with RA and 120 healthy subjects. Genomic DNA was extracted from whole blood, and gene polymorphism was tested using a tetra-primer amplification refractory mutation system-polymerase chain reaction. The results demonstrated that LGALS3 rs4652 AC genotype increased the risk of RA (OR=11.622, 95% CI=4.473-28.656; P=0.001) when compared with the AA genotype. However, the CC genotype and the C allele were not associated with RA. These findings indicated an association between LGALS3 rs4652 variation and the risk of RA in a sample of Iranian individuals. Further studies with larger sample sizes and populations of different ethnicities are required to validate our findings.
... In addition, GDF-15 influences the metabolism of carbohydrates and lipids. It plays multiple roles in va rious pathologies such as cardiovascular disease, obesity, inflammation, and cancer due to its anti-inflammatory and antiproliferative properties 10,11 . Previous studies have shown that GDF-15 is up regu lated in the atherosclerotic vessel wall and GDF--15 is associated with infarct size in experimental heart attack models [7][8][9][10][11][12] . ...
... It plays multiple roles in va rious pathologies such as cardiovascular disease, obesity, inflammation, and cancer due to its anti-inflammatory and antiproliferative properties 10,11 . Previous studies have shown that GDF-15 is up regu lated in the atherosclerotic vessel wall and GDF--15 is associated with infarct size in experimental heart attack models [7][8][9][10][11][12] . It has been reported that GDF-15 immunoreactivity is localized in macrophages of atherosclerotic carotid arteries and co-localizes with oxidized low-density lipoproteins. ...
Objectives:
Growth differentiation factor (GDF)-15 was originally identified as a factor secreted by activated macrophages, and plays an important role in cell growth and differentiation. GDF-15 plays an important role in cell growth, signal transduction, and apoptosis regulation. The aim of this study was to evaluate the serum GDF-15 levels and their relationship with disease-related characteristics in patients with rheumatoid arthritis (RA).
Materials and methods:
Forty-six patients diagnosed with RA and 36 demographically matched healthy control subjects participated in this study. GDF-15 levels were measured in blood samples from patients and controls. The disease activity score-28 (DAS28) was used to evaluate the disease activity of RA. The quality of life was evaluated using the disease-specific rheumatoid arthritis quality of life (RAQoL) scale. The health assessment questionnaire (HAQ) was used to evaluate the functional status. The degree of joint damage was assessed according to Larsen's method. Atherosclerosis was assessed by a cardiologist with the help of echocardiography according to the carotid intima media thickness (CIMT) method; vascular stiffness was assessed by using the flow mediated dilatation (FMD) method.
Results:
Serum GDF-15 levels were significantly higher in RA patients when compared to the control subjects (p< 0.05). RA patients were divided into two groups according to the disease activity; while 26 subjects (57%) were in the active group, 20 patients were in the non-active group (43%). Serum GDF-15 levels were significantly higher in the group that was considered to have an active disease. According to Pearson's correlation, serum GDF-15 levels were positively correlated with erythrocyte sedimentation rate (ESR) levels, morning stiffness, DAS28 score, tender joint count, and CIMT (p.
