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, GNPDA2, LEPR, MC4R, NEGR1, NPY, PPARG, TMEM18, and UCP2 were determined, and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Results: Analysis revealed an association between the G allele of the rs1137101 polymorphism (LEPR gene) and obesity risk (OR: 3.30 (1.45; 7.50), p = 0.004) in the early-onset group of psoriatic patients. Furthermore, the T allele of rs925946 polymorphism (BDNF gene) was also associated with increased risk of obesity in early-onset psoriasis (OR: 2.26 (1.24; 4.14) p = 0.008). Conclusions: Our results suggest that in psoriatic patients, there are prominent differences in the causes of obesity that should be accounted for, including not only environmental factors but also patient characteristics, such as the time of disease onset as well as genetic factors.

Casual association between childhood body mass index and risk of psoriasis: A Mendelian randomization study

“…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.…”

“…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.…”

Considerations of the Genetic Background of Obesity among Patients with 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 ].…”