Association of cardiovascular and metabolic disease genes with psoriasis.
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ABSTRACT:
SUBMITTER: Lu Y
PROVIDER: S-EPMC3570714 | biostudies-literature | 2013 Mar
REPOSITORIES: biostudies-literature
Publications
Association of cardiovascular and metabolic disease genes with psoriasis.
Lu Yingchang Y Chen Haoyan H Nikamo Pernilla P Qi Low Hui H Helms Cynthia C Seielstad Mark M Liu Jianjun J Bowcock Anne M AM Stahle Mona M Liao Wilson W
The Journal of investigative dermatology 20121129 3
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Project description:Background A large number of observational studies showed that patients with psoriasis have a higher risk of cardiovascular disease (CVD), but most studies did not fully adjust for confounding factors, so it is not clear whether the risk of CVD is directly attributed to psoriasis. We used Mendelian randomization (MR) to evaluate the potential causal relationship between psoriasis and CVD. Methods We used genetic instruments from the genome-wide association study (GWAS) of European descent for psoriasis to investigate its relationship with CVD. Inverse variance-weighted (IVW) MR analyses were used for the primary analysis. In addition, a variety of other methods were used to replicate the analysis. Results The fixed-effects IVW method indicated that genetic susceptibility to psoriasis was associated with a higher risk of heart failure (HF) [odds ratio (OR) = 1.04; 95% CI, 1.01–1.06, P = 2.72E-03], atrial fibrillation (AF) (OR = 1.04; 95% CI, 1.02–1.07, P = 3.27E-04), myocardial infarction (MI) (OR = 1.07; 95% CI, 1.01–1.12, P = 0.01), valvular heart disease (VHD) (OR = 1.001; 95% CI, 1.000–1.002, P = 1.85E-03), and large artery stroke (LAS) (OR = 1.11; 95% CI, 1.05–1.18, P = 5.37E-04) but not with the other two subtypes of ischemic stroke (IS) [cardioembolic stroke (CES) (OR = 1.03; 95% CI, 0.98–1.07, P = 0.27) and small vessel stroke (SVS) (OR = 1.00; 95% CI, 0.95–1.07), P = 0.88)]. Sensitivity analysis found weak evidence of horizontal diversity and heterogeneity to ensure the stability of the results. Conclusion Our study provided evidence for a potential causal link between psoriasis and CVD. These findings partly suggest that early monitoring of cardiovascular risk in patients with psoriasis is intentional.
| S-EPMC9278135 | biostudies-literature
Project description: Not available
| S-EPMC7929566 | biostudies-literature
Project description:The role of metabolic disturbance in polycystic ovary syndrome (PCOS) has been well established, with insulin resistance and the resulting compensatory hyperinsulinemia thought to promote hyperandrogenemia. Genome-wide association studies (GWAS) have established a large number of loci for metabolic conditions such as type 2 diabetes and obesity. A subset of these loci has been investigated for a role in PCOS; these studies generally have not revealed a confirmed role for these loci in PCOS risk. However, a large scale investigation of genes related to these pathways has not previously been performed. We conducted a two stage case control association study of 121,715 single nucleotide polymorphisms (SNPs) selected to represent susceptibility loci associated with traits such as type 2 diabetes, obesity measures, lipid levels and cardiovascular function using the Cardio-Metabochip in 847 PCOS cases and 845 controls. Several hypothesis-generating associations with PCOS were observed (top SNP rs2129107, P=3.8×10(-6)). We did not find any loci definitively associated with PCOS after strict correction for multiple testing, suggesting that cardio-metabolic loci are not major risk factors underlying the susceptibility to PCOS.
| S-EPMC3689580 | biostudies-literature
Project description:Purpose of reviewPsoriasis is a chronic inflammatory skin condition that is associated with increased cardiovascular risk compared to those without psoriasis. This review will cover emerging mechanisms of cardiovascular risk, key pathways targeted with biologic therapies, and the current evidence on therapies to modulate this risk in patients with psoriasis.Recent findingsRecent scientific work has highlighted mechanisms that contribute to this enhanced risk, including the role of vascular endothelial dysfunction, platelet activation, dyslipidemia, and increased cardiometabolic comorbidities. Newer biologic and targeted synthetic therapies have transformed psoriasis treatment with high rates of clinical remission and durable skin disease control now possible. Epidemiological evidence suggests that many of these therapies may lower cardiovascular risk in psoriasis, although prospective interventional data is lacking (or mixed). Recently, caution has also been raised that some treatments may negatively affect cardiovascular risk. Overall, the current data suggests a positive or neutral ability to reduce cardiovascular risk for TNF, IL-17A, and IL-12/23p40 inhibitors, but current evidence remains conflicting for anti-IL-23/p19 and JAK inhibitors. More studies that include prospective cohorts, larger number of patients, treatment duration, and validated surrogate outcomes are needed to better evaluate the role of biologic therapies on cardiovascular risk in psoriasis.
| S-EPMC9744099 | biostudies-literature
Project description:IntroductionClark (1996) proposed that abnormal blood flow is related to some congenital cardiovascular malformations (CCVMs), particularly CCVM with obstruction to blood flow. Our hypothesis is that CCVMs may relate to genes that affect blood coagulation or flow. We studied whether polymorphisms of such genes are related to CCVMs; previous association of these SNPs to conotruncal CCVMs is described.MethodsWe assessed risk of pulmonary stenosis (PS, N = 120), atrial septal defect (ASD, N = 108), aortic stenosis (AS, N = 36), and coarctation of the aorta (CoAo, N = 64), associated with 33 candidate genes, selected for their relationship to blood flow affected by homocysteine metabolism, coagulation, cell-cell interaction, inflammation, or blood pressure regulation.ResultsEffects were specific to cardiac phenotype and race. CoAo was associated with MTHFR (-667) C>T (odds ratio [OR] for TT 3.5, 95% confidence limits [CI] 1.4-8.6). AS was associated with a polymorphism of SERPINE1, G5>G4, OR = 5.6 for the homozygote with 95% CI 1.4-22.9. Unique polymorphisms were associated with increased risk of ASD and PS: NPPA 664G>A with ASD (OR of 2.4, 95%CI 1.3-4.4) and NOS3 (-690) C>T with PS (OR 6.1; 95% CI 1.6-22.6 in the African American population only). For ASD, the NPPA (-664) G>A SNP there was increased risk from the variant genotype only in maternal smokers (OR 2.6; 95% CI 1.0-7.2).ConclusionsGenes affecting vascular function and coagulation appear to be promising candidates for the etiology of cardiac malformations and warrant further study.
| S-EPMC2857411 | biostudies-literature
Project description:Obesity, metabolic syndrome (MetS), and psoriasis, largely driven by environmental factors, show multiple bidirectional associations, with important metabolic implications in psoriatic patients. Besides body mass index (BMI) as a measure of obesity, data on phase angle (PhA), a direct measure by bioelectrical impedance analysis (BIA), used as a marker of cellular health and a predictor of morbidity and mortality in various diseases, are still lacking in psoriasis. In this case-control, cross-sectional study, we investigated the PhA in 180 pairs of adult psoriatic patients and healthy controls, evaluating also the potential use of the PhA as marker of the clinical severity, the quality of life, and the presence of the MetS in psoriatic patients.Anthropometric measures, metabolic profile and bioelectrical variables were evaluated. The clinical severity was assessed by standardized psoriasis area and severity index (PASI) score and c-reactive protein (CRP) levels, and the quality of life was evaluated by dermatology life quality index (DLQI). MetS was diagnosed according to Adult Treatment Panel III.Psoriatic patients presented smaller PhA (p < 0.001) and higher prevalence MetS compared with controls. The PhA was significantly associated with number of parameters of MetS in both groups (p < 0.001). After adjusting for BMI, this association remained significant in psoriatic patients only (p < 0.001). Among psoriatic patients, the PhA was the major index value for the diagnosis of MetS (OR 5.87, 95 % CI 5.07-6.79) and was inversely associated with both PASI score and DLQI, independently of BMI (p < 0.001). At multiple regression analysis, the PhA well predicted the PASI score and DLQI. Based on ROC curves, the most sensitive and specific cutoffs of PhA to predict the highest PASI score and the lowest DQLI were ?4.8° and ?4.9°, respectively.We reported that psoriatic patients presented small PhAs, with a novel association between PhA, clinical severity, quality of life in psoriatic patients, and MetS. Further studies are required to validate the PhA's prognostic ability in assessing the clinical severity and MetS in psoriatic patients.
| S-EPMC4863378 | biostudies-literature
Project description:Psoriasis is a chronic inflammatory disease believed to be correlated with numerous cardiovascular risk factors including increased blood pressure, elevated blood cholesterol level, diabetes, inactivity, high body mass index (obesity) and dyslipidaemia. The present meta-analysis intends to assess the association between psoriasis and cardiovascular risk factors. Three hundred and fifty articles were primarily screened using NCBI MEDLINE/PubMed and Cochrane library from its inception until June 30, 2018. Of these, 26 observational studies depending upon the inclusion and exclusion criteria were included in the study with 17,672 psoriasis patients and 66,407 non-psoriasis subjects. The psoriasis patients were found to be at significantly increased risk of systolic blood pressure (SBP) [ORs 2.31 (95% CI 1.12, 4.74)], diastolic blood pressure (DBP) [ORs 2.31 (95% CI 1.58, 3.38)], abdominal obesity [ORs 1.90 (95% CI 1.45, 2.50)] and triglycerides [ORs 1.80 (95% CI 1.29, 2.51)] as compared to non-psoriasis subjects. The subgroup analyses of studies based on the continents revealed that psoriasis patients from Middle East are prone to higher risk factors of CVD including increased levels of triglyceride, cholesterol, DBP, SBP, fasting blood sugar, body mass index and decreased HDL levels, whereas psoriasis patients from European population reported increased LDL-C and waist circumference. The present study supports a significant association between psoriasis and incidence of major adverse cardiovascular events. Contrary to the previous literature, our finding suggests that hypertension is a highly associative condition in psoriasis. The findings of this study could be validated amongst well-defined cohorts of patients with psoriasis individually in different regions to confirm the implication of the study.
| S-EPMC7007463 | biostudies-literature
Project description:Cholinergic neurotransmission in the central and autonomic nervous systems regulates immediate variations in and longer-term maintenance of cardiovascular function with acetylcholinesterase (AChE) activity that is critical to temporal responsiveness. Butyrylcholinesterase (BChE), largely confined to the liver and plasma, subserves metabolic functions. AChE and BChE are found in hematopoietic cells and plasma, enabling one to correlate enzyme levels in whole blood with hereditary traits in twins. Using both twin and unrelated subjects, we found certain single nucleotide polymorphisms (SNPs) in the ACHE gene correlated with catalytic properties and general cardiovascular functions. SNP discovery from ACHE resequencing identified 19 SNPs: 7 coding SNPs (cSNPs), of which 4 are nonsynonymous, and 12 SNPs in untranslated regions, of which 3 are in a conserved sequence of an upstream intron. Both AChE and BChE activity traits in blood were heritable: AChE at 48.8 ± 6.1% and BChE at 81.4 ± 2.8%. Allelic and haplotype variations in the ACHE and BCHE genes were associated with changes in blood AChE and BChE activities. AChE activity was associated with BP status and SBP, whereas BChE activity was associated with features of the metabolic syndrome (especially body weight and BMI). Gene products from cDNAs with nonsynonymous cSNPs were expressed and purified. Protein expression of ACHE nonsynonymous variant D134H (SNP6) is impaired: this variant shows compromised stability and altered rates of organophosphate inhibition and oxime-assisted reactivation. A substantial fraction of the D134H instability could be reversed in the D134H/R136Q mutant. Hence, common genetic variations at ACHE and BCHE loci were associated with changes in corresponding enzymatic activities in blood.
| S-EPMC3126649 | biostudies-literature
Project description:ImportanceThe epidemiological link between immune-mediated diseases (IMIDs) and cardiovascular disease has often been attributed to systemic inflammation. However, the direction of causality and the biological mechanisms linking cardiovascular disease with IMIDs are incompletely understood. Given the robust epidemiological association and the growing body of supportive mechanistic evidence, psoriasis is an exemplary IMID model for exploring this relationship.ObjectiveTo assess the bidirectional relationships between genetic predictors of psoriasis and the 2 major forms of cardiovascular disease, coronary artery disease (CAD) and stroke, and to evaluate the association between genetic predictors of cardiovascular disease with 9 other IMIDs.Design, setting, and participantsThis was a genetic association study using mendelian randomization (MR), a powerful genetic tool to help distinguish causation from associations observed in epidemiological studies, to provide supportive evidence for causality between traits. The study conducted 2-sample MR analyses using summary-level data from large-scale genome-wide association meta-analysis studies (GWAS) for each trait. The analysis focused on individuals of European descent from GWAS meta-analyses, involving CAD, stroke, psoriasis, and 9 other IMIDs. Data were analyzed from January 2023 to May 2024.ExposuresGenetic predictors of CAD, stroke, psoriasis, and 9 other IMIDs.Main outcomes and measuresThe primary outcomes were the associations of genetic predictors of CAD and stroke with the risk of psoriasis and 9 other IMIDs, determined using inverse-variance weighted (IVW) MR estimates.ResultsThis study included 181 249 cases and 1 165 690 controls with CAD, 110 182 cases and 1 503 898 controls with stroke, 36 466 cases and 458 078 controls with psoriasis, for a total of approximately 3 400 000 individuals, and 9 other IMIDs. In contrast to previous assumptions, genetic predictors of psoriasis were found to have no association with CAD or stroke. In the reverse direction, genetic predictors of both CAD (MR estimate IVW odds ratio [OR], 1.07; 95% CI, 1.04-1.10; P = .003) and stroke (IVW OR, 1.22; 95% CI, 1.05-1.41; P = .01) were found to have risk-increasing associations with psoriasis. Adjusting for stroke rendered the associations of genetically predicted CAD with psoriasis risk nonsignificant (and vice versa), suggesting that a shared effect underlying genetic risk for CAD and stroke associates with increased psoriasis risk. No risk-increasing associations were observed for genetic predictors of cardiovascular disease with other common IMIDs, including rheumatoid arthritis and inflammatory bowel disease.Conclusions and relevanceFindings of this mendelian randomization study indicate that genetic predictors of cardiovascular disease were associated with increased psoriasis risk with no reciprocal effect or association with other IMIDs. Elucidating mechanisms underpinning this association could lead to novel therapeutic approaches in both diseases.
| S-EPMC11411451 | biostudies-literature
Project description:BackgroundThe skin-gut axis, characterized by bidirectional communication between the skin and gut, plays a crucial role in the pathogenesis of psoriasis and inflammatory bowel diseases (IBD).ObjectivesWe aimed to explore the association between psoriasis and IBD and identify predictors associated with IBD development among patients with psoriasis.DesignRetrospective cohort study.MethodsA retrospective study which utilized an electronic database from the Meuhedet Health Maintenance Organization (MHMO) in Israel. Psoriasis was categorized as severe if any systemic agent or phototherapy was administered. Univariate and multivariate logistic regressions were used to identify specific predictors for IBD, with adjustments made for potential confounders. The study received approval from the Ethical Committee of the MHMO.ResultsIn total, 61,003 adult patients who were diagnosed with psoriasis between 2000 and 2022 were included. Among them, 1495/61,003 patients (2.4%) were diagnosed with IBD, as compared to 3834/244,012 patients (1.6%) in the non-psoriasis group [adjusted odds ratio (OR): 1.47; 95% confidence interval (CI): 1.37-1.56; p < 0.001]. Increased age (OR: 1.01; 95% CI: 1.01-1.02; p < 0.001), male gender (OR: 1.22; 95% CI: 1.03-1.45; p = 0.024), and Jewish ethnicity (OR: 2.5; 95% CI: 1.2-4.1; p < 0.001) were identified as significant risk factors for IBD. Spondyloarthropathies, including psoriatic arthritis (OR: 2.27; 95% CI: 1.86-2.77; p < 0.001) and ankylosing spondylitis (OR: 2.82; 95% CI: 1.5-5.32; p < 0.05), were associated with a higher prevalence of IBD. Furthermore, severe psoriasis was significantly associated with a higher likelihood of IBD, compared to mild psoriasis (OR: 16.03; 95% CI: 11.02-23.34; p < 0.001).ConclusionA significant association between psoriasis and IBD was demonstrated, including its subtypes: Crohn's disease and ulcerative colitis. Moreover, such association may depend on psoriasis severity as determined by the treatment used. This association warrants further investigation and implies a potential need for closer monitoring of patients with severe psoriasis.
| S-EPMC10822082 | biostudies-literature