Leptin Receptor (rs1137101) and Brain-Derived Neurotrophic Factor (rs925946) Gene Variants Are Associated with Obesity in the Early- but Not in the Late-Onset Population of Hungarian Psoriatic Patients
Abstract:Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a population-based case-control study including 3541 subjects (574 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 20 SNPs at ADIPOQ, BDNF, FTO, GNPDA… Show more
“…Kim et al demonstrated that individuals with a BMI of 30 units had a considerably higher risk of psoriasis than those with a BMI of 18.5–23.0 unites (HR = 1.09, 95% confidence interval: 1.06–1.11) 22 . Szentkereszty‐Kovács et al found that the leptin receptor (rs1137101) and brain‐derived neurotrophic factor (rs925946) gene alterations are present in those individuals with psoriasis, suggesting that obesity and psoriasis may share a common genetic background 23 . In response to inflammatory agents such as TNF‐ and IL‐1, leptin levels in adipose tissue increase, mediating obesity‐associated inflammation and playing a role in the development of psoriasis.…”
Section: Discussionmentioning
confidence: 99%
“…Although the MR estimations obtained from IVW, weighted median, and MR-Egger regression were not entirely consistent, both IVW and weighted median methods provide evidence suggesting that obesity and psoriasis may share a common genetic background. 23 In response to inflammatory agents such as TNFand IL-1, leptin levels in adipose tissue increase, mediating obesityassociated inflammation and playing a role in the development of psoriasis. Reduced levels of lipocalin in obese psoriasis patients result in a chronic inflammatory state.…”
Section: Heterogeneity and Sensitivity Testmentioning
BackgroundObservational studies have suggested that childhood body mass index (BMI) is associated with the risk of psoriasis. However, their causal relationship remains unclear. In this investigation, we aimed to determine whether an association exists between childhood BMI and psoriasis.MethodsUsing summary statistics for childhood BMI of European descent from publicly available GWAS meta‐analyses (n = 39 620), we conducted Mendelian randomization (MR) research using the inverse variance weighting (IVW), weighted median, and MR‐Egger regression techniques. The outcome was a genome‐wide association studies (GWAS) for the self‐reported non‐cancer disease classification psoriasis in the UK Biobank population (total n = 337 159; case = 3871; control = 333 288).ResultsWe selected instrumental variables from 16 single‐molecule polymorphisms that attained genome‐wide significance in GWAS on childhood BMI. Using the IVW method, our findings supported a causal relationship between childhood BMI and psoriasis (beta = 0.003, standard error [SE] = 0.001, p = 0.006). Using MR‐Egger regression analysis, we evaluated the potential for directional pleiotropy to bias our results (intercept = 0.00039, p‐value = 0.247) and found no causal relationship between childhood BMI and psoriasis (beta = −0.002, SE = 0.004, p = 0.625). The weighted median method, however, provided proof of a causal relationship (beta = 0.003, SE = 0.001, p = 0.029). Cochran's Q test and the funnel plot revealed little proof of heterogeneity or asymmetry, indicating the lack of directional pleiotropy.ConclusionAccording to the findings of the MR analysis, an increased childhood BMI may be linked to a higher likelihood of psoriasis.
“…Kim et al demonstrated that individuals with a BMI of 30 units had a considerably higher risk of psoriasis than those with a BMI of 18.5–23.0 unites (HR = 1.09, 95% confidence interval: 1.06–1.11) 22 . Szentkereszty‐Kovács et al found that the leptin receptor (rs1137101) and brain‐derived neurotrophic factor (rs925946) gene alterations are present in those individuals with psoriasis, suggesting that obesity and psoriasis may share a common genetic background 23 . In response to inflammatory agents such as TNF‐ and IL‐1, leptin levels in adipose tissue increase, mediating obesity‐associated inflammation and playing a role in the development of psoriasis.…”
Section: Discussionmentioning
confidence: 99%
“…Although the MR estimations obtained from IVW, weighted median, and MR-Egger regression were not entirely consistent, both IVW and weighted median methods provide evidence suggesting that obesity and psoriasis may share a common genetic background. 23 In response to inflammatory agents such as TNFand IL-1, leptin levels in adipose tissue increase, mediating obesityassociated inflammation and playing a role in the development of psoriasis. Reduced levels of lipocalin in obese psoriasis patients result in a chronic inflammatory state.…”
Section: Heterogeneity and Sensitivity Testmentioning
BackgroundObservational studies have suggested that childhood body mass index (BMI) is associated with the risk of psoriasis. However, their causal relationship remains unclear. In this investigation, we aimed to determine whether an association exists between childhood BMI and psoriasis.MethodsUsing summary statistics for childhood BMI of European descent from publicly available GWAS meta‐analyses (n = 39 620), we conducted Mendelian randomization (MR) research using the inverse variance weighting (IVW), weighted median, and MR‐Egger regression techniques. The outcome was a genome‐wide association studies (GWAS) for the self‐reported non‐cancer disease classification psoriasis in the UK Biobank population (total n = 337 159; case = 3871; control = 333 288).ResultsWe selected instrumental variables from 16 single‐molecule polymorphisms that attained genome‐wide significance in GWAS on childhood BMI. Using the IVW method, our findings supported a causal relationship between childhood BMI and psoriasis (beta = 0.003, standard error [SE] = 0.001, p = 0.006). Using MR‐Egger regression analysis, we evaluated the potential for directional pleiotropy to bias our results (intercept = 0.00039, p‐value = 0.247) and found no causal relationship between childhood BMI and psoriasis (beta = −0.002, SE = 0.004, p = 0.625). The weighted median method, however, provided proof of a causal relationship (beta = 0.003, SE = 0.001, p = 0.029). Cochran's Q test and the funnel plot revealed little proof of heterogeneity or asymmetry, indicating the lack of directional pleiotropy.ConclusionAccording to the findings of the MR analysis, an increased childhood BMI may be linked to a higher likelihood of psoriasis.
“…Moreover, a population-based case control study among 574 psoriasis subjects of Hungarian origin demonstrated the link between the LEPR gene polymorphism (rs1137101) and obesity prevalence among patients with early disease onset. Multiple single-nucleotide polymorphisms were genotyped in the study, such as ADIPOQ , FTO , PPARG and FTO ; however, no prominent associations were found [ 64 ]. Mitsuyama et al described the significant association between leptin mRNA expression in subcutaneous adipose tissue among psoriatic patients and serum leptin levels, disease severity and obesity [ 65 ].…”
Section: Potential Common Genetic Background Of Obesity Among Psoriat...mentioning
Psoriasis comorbidities may emerge from pleiotropic mechanisms, including common proinflammatory pathways, cellular mediators or genetic predisposition. Obesity is considered to be an independent risk factor of psoriasis, which may influence the severity of the disease and its early onset, decrease patients’ quality of life, alter response to psoriasis therapies and affect morbidity by reduced life expectancy due to cardiovascular events. Although novel approaches, including genetic techniques, have provided a wide range of new research, there are still scarce studies elaborating on the common genetic background of psoriasis and obesity. The aim of this study was to present and evaluate a possible common genetic background of psoriasis and concomitant increased body mass based on the review of the available literature.
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