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.

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.

Alcohol in Psoriasis-From Bench to Bedside.

Alcohol affects the symptoms, compliance and comorbidities as well as the safety and efficacy of treatments in psoriatic patients. In this review, we aim to summarize and link clinical observations with a molecular background, such as signaling pathways at the cellular level and genetic variations, and to provide an overview of how this knowledge could influence our treatment selection and patient management.

The prevalence of ADH1B and OPRM1 alleles predisposing for alcohol consumption are increased in the Hungarian psoriasis population.

Alcohol intake affects in great the symptoms and life of  psoriasis patients, although the association of SNPs related to increased alcohol consumption with psoriasis has not been elucidated. Therefore, to investigate the association of psoriasis with established alcohol consumption and dependence-related gene variants we conducted a population-based case-control study including 3743 subjects (776 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 23 SNPs at ADH1B, ADH1C, ALDH1A1, ALDH2, SLC6A3, DDC, GABRA2, GABRG1, HTR1B, MAOA, TPH2, CHRM2, GRIN2A, POMC, OPRM1, OPRK1 and BDNF were determined and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Analysis revealed association between C allele of the rs1229984 polymorphism (ADH1B gene) and psoriasis risk (ORadditive = 1.58, 95% CI 1.23-2.03, p < 0.001, ORrecessive = 1.58, 95% CI 1.22-2.04, p = 0.001). Furthermore, the G allele of rs1799971 polymorphism (OPRM1 gene) increased the risk of familial aggregation (ORadditive = 1.99, 95% CI 1.36-2.91, p < 0.001 ORdominant = 2.01, 95% CI 1.35-3.01, p < 0.001). In subgroups of psoriatic patients with history of early onset and familial aggregation effect allele 'C' of rs1229984 showed association in the additive and recessive models (ORadditive = 2.41, 95% CI 1.26-4.61, p < 0.01, ORrecessive = 2.42, 95% CI 1.26-4.68, p < 0.01). While effect allele 'G' of rs1799971 (OPRM1) also associated with increased risk of early onset and familial aggregation of psoriasis in the additive and dominant models (ORadditive = 1.75, 95% CI 1.27-2.43, p = 0.001, ORdominant = 1.82, 95% CI 1.26-2.63, p = 0.001). Our results suggest that genetically defined high-risk individuals for alcohol consumption are more common in the psoriasis population.

Genome wide analysis of TLR1/2- and TLR4-activated SZ95 sebocytes reveals a complex immune-competence and identifies serum amyloid A as a marker for activated sebaceous glands.

Toll-like receptors (TLR) 2 and 4 are active in sebaceous glands and play a central role in the development of acne. Still, there is only limited knowledge on their effect on sebocytes. In this work we performed global gene expression profile analysis with functional clustering of the differentially regulated genes of TLR1/2 (PAM3CSK4)- and TLR4 (lipopolysaccharide [LPS])-activated SZ95 sebocytes. Both TLR1/2- and 4-activation promoted inflammation in a similar manner already at an early time-point (6 hours), regulating genes involved in inflammation, wound healing and chemotaxis reflecting a more complex cytokine and chemokine regulation than previously known. Importantly, lipid metabolism, the primary feature of sebocytes, was affected at the level of gene expression only at a later time point (24 hours) indicating that sebocytes prioritize to exert a pro-inflammatory phenotype when confronted with a danger signal. Supporting the biological relevance of our results, a meta-analysis revealed that the genes showing the strongest up-regulation were also found up-regulated in acne. Of these genes, serum amyloid A 1/2 (SAA1/2) was confirmed to be a suitable protein marker for in vivo activated sebocytes, underlining their immune-competence, which is structurally defined within sebaceous glands of acne and rosacea skin samples. Altogether our findings demonstrate that sebocytes are not only positioned at the end point of inflammation but are actively involved in shaping the inflammatory response with putative diagnostic and therapeutic relevance.

Different accumulation of free amino acids during short- and long-term osmotic stress in wheat.

The effect of wheat chromosome 5A on free amino acid accumulation induced by osmotic stress was compared in chromosome 5A substitution lines with different freezing tolerance. Treatment with 15% polyethylene glycol (PEG) resulted in greater total free amino acid content even after 3 days compared to the controls. The ratio of amino acids belonging to various amino acid families differed after 3-week treatment in the control and PEG-treated plants only in the case of the freezing-sensitive substitution line. There was a transient increase with a maximum after 3 days in the amounts of several amino acids, after which their concentrations exhibited a more gradual increase. During the first days of osmotic stress the Glu, Gln, Asp, Asn, Thr, Ser, Leu, and His concentrations were greater in the tolerant substitution line than in the sensitive one, while the opposite relationship was observed at the end of the PEG treatment. The coordinated changes in the levels of individual amino acids indicated that they are involved in both the short- and long-term responses to osmotic stress. The alterations differed in the two chromosome 5A substitution lines, depending on the stress tolerance of the chromosome donor genotype.

Differential effects of cold acclimation and abscisic acid on free amino acid composition in wheat.

The effect of cold acclimation and abscisic acid (ABA) treatment on the free amino acid composition was compared in Chinese Spring chromosome 5A substitution lines with different levels of freezing tolerance. The total amino acid content gradually increased during the 3-week cold acclimation period, while the effect of ABA became visible only after 7 d. The ratio of members of the glutamate family increased during cold acclimation and the ratio of amino acids belonging to the aspartate family decreased. Opposite changes were observed after treatment with ABA. Consistently with these results, ABA only induced a major increase in the Asn content, while the Asp, Glu, Gln and Pro levels were greatly induced by cold. A corresponding alteration at the gene expression level was only found for Pro and Glu. With the exception of Pro, cold- or ABA-induced changes in the amino acid levelsor Pro, did not correlate with the freezing tolerance of the three genotypes examined and were not affected by chromosome 5A. Since cold acclimation induced the accumulation of most of the amino acids, while ABA had a significant effect only on Asn, the cold-induced changes in free amino acid levels were probably not mediated by ABA.

Differential effects of cold, osmotic stress and abscisic acid on polyamine accumulation in wheat.

The effects of cold, osmotic stress and abscisic acid (ABA) on polyamine accumulation were compared in the moderately freezing-sensitive wheat (Triticum aestivum L.) variety Chinese Spring (CS) and in two derived chromosome 5A substitution lines, CS(T. spelta 5A) and CS(Cheyenne 5A), exhibiting lower and higher levels of freezing tolerance, respectively. When compared with the other treatments, putrescine (Put) and spermidine (Spd) levels were much greater after cold treatment, spermine (Spm) following polyethylene glycol-induced (PEG) osmotic stress and Spm and cadaverine (Cad) after ABA treatment. During 3-week cold stress, the Put concentration, first exhibited a transient increase and decrease, and then gradually increased. These alterations may be due to changes in the expression of genes encoding the enzymes of Put synthesis. The Put content was higher in the freezing-tolerant chromosome 5A substitution line than in the sensitive one after 3 weeks of cold. In contrast to cold, ABA and PEG induced a continuous decrease in the Spd level when applied for a period of 3 weeks. The Spm content, which increased after PEG and ABA addition, was twice as high as that of Put during ABA treatment at most sampling points, but this difference was lower in the case of PEG. The Cad level, induced to a great extent by ABA, was much lower when compared with that of the other polyamines. The present experiments indicate that cold, osmotic stress and ABA have different effects on polyamines, and that some of these changes are affected by chromosome 5A and correlate with the level of stress tolerance.