Biological Sex and IgE Sensitization Influence Severity of Depression and Cortisol Levels in Atopic Dermatitis.

BACKGROUND: Depression is a common comorbid condition with atopic dermatitis (AD), particularly during the active disease cycle. Controversial results regarding the contribution of biological sex, immunoglobulin E (IgE) sensitization, and cortisol on AD severity and comorbid depression justify further investigation. OBJECTIVE AND METHODS: To explore the influence of sex and IgE sensitization on biochemical and psychological parameters, and severity of AD, a case-control study of 105 volunteers (56 AD, 49 healthy controls (HC); 50 males, 55 females) was conducted over 10 weeks, starting at dermatological symptom onset. Disease severity, serum IgE, cortisol and testosterone levels, and depression scores were assessed at study baseline and after 10 weeks of conventional treatment. RESULTS: Dermatological severity differed among AD males by IgE sensitization and was elevated in males with extrinsic atopic dermatitis (EAD). Hamilton Depression Rating Scale (HAMD) scores were elevated in all patients at study baseline and improved with symptom reduction to HC levels, except female EAD. Severity of depression and dermatitis were correlated in EAD males at baseline and at week 10. Serum cortisol was elevated in male EAD at baseline, in contrast to males with intrinsic atopic dermatitis (IAD) at week 10. In addition, cortisol levels were found negatively correlated with SCORAD and HAMD scores in EAD males at week 10. CONCLUSION: Pathophysiological features of AD and depression are likely related to different inflammation-based effects and appear to be biological sex-dependent. Cortisol levels depend on biological sex and IgE sensitization in AD and increase in males with EAD at exacerbation and IAD males at resolution. Biological sex-related disease triggers, IgE sensitization, and cortisol levels are important for the understanding of the mechanisms underlying AD and comorbid depression.

Fast detection of deletion breakpoints using quantitative PCR.

The routine detection of large and medium copy number variants (CNVs) is well established. Hemizygotic deletions or duplications in the large Duchenne muscular dystrophy DMD gene responsible for Duchenne and Becker muscular dystrophies are routinely identified using multiple ligation probe amplification and array-based comparative genomic hybridization. These methods only map deleted or duplicated exons, without providing the exact location of breakpoints. Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. Here, we present a strategy for detecting the breakpoints of medium and large CNVs regardless of their size. The hemizygous deletion of exons 45-50 in the DMD gene and the large autosomal heterozygous PARK2 deletion were used to demonstrate the workflow that relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation. The strategy is fast, reliable and cost-efficient, making it amenable to widespread use in genetic laboratories.

Polymorphic genetic markers and how they are associated with clinical and metabolic indicators of type 2 diabetes mellitus in the Kazakh population.

BACKGROUND: Type 2 diabetes mellitus is a serious public health problem worldwide. The aim of the study was to analyze the relationship of eight polymorphic gene variants with the development of clinical-metabolic rates of type 2 diabetes mellitus inside Kazakh population. MATERIALS AND METHODS: 139 patients with type 2 diabetes mellitus and 100 patients in the control group were examined. Genotyping of polymorphisms of candidate genes was carried out on a next generation QuantStudio 12 K Flex unit. RESULTS: Gene TCF7L2 locus rs7901695 and rs7903146, gene KCNQ1 locus rs2237892, rs7756992, and gene CDKAL1 locus rs7754840 demonstrated statistically significant associations with glucose metabolism, lipid profile and body mass index (BMI) in type 2 DM inside the population. Statistically significant difference in anthropometric and biochemical measures of rs17584499, rs4712523 and rs163184 has not been revealed. CONCLUSIONS: Genetic polymorphisms that influence pancreatic gland beta-cells insulin release and secretion associate with metabolic and anthropometric measures definitive for type 2 DM in Kazakh population.

Seasonality and BDNF polymorphism influences depression outcome in patients with atopic dermatitis and psoriasis.

OBJECTIVES: To examine the effect of seasonality and rs6265 genotype on depression outcome and brain-derived neurotrophic factor (BDNF) level with dermatitis patients from onset through remission. METHODS: Atopic dermatitis (AD, 56) and psoriasis (PS, 33) patients and healthy controls (HC, 49) were recruited over the 2014 calendar year. Patients were subdivided by immunoglobulin E (IgE) sensitivity (AD only), season and rs6265 genotype. Assessments were performed at onset and week 10 (Hamilton Depression Rating Scale [HAM-D], SCORAD/PASI, IgE, BDNF). Patients received standard corticosteroid and antihistamine interventions. RESULTS: All patients responded to corticosteroid treatment. Seasonally differential outcomes were observed in all groups. HAM-D was elevated at onset and improved over 10 weeks: AD cohort 1 (autumn/winter, AD-1) patients improved and AD cohort 2 (spring/summer, AD-2) patients remained elevated. BDNF levels were elevated in AD and seasonal differential: AD-2 declined at 10 weeks, whereas AD-1 remained high (intrinsic AD) or elevated further (extrinsic AD). PS cohort 2 declined to below control at 10 weeks. AD Val/Val had persistently elevated HAM-D and AD Val/Met were either normal (AD-1) or persistently elevated (AD-2). CONCLUSIONS: Findings presented here suggest a strong influence of seasonality on depression outcome and BDNF expression in AD and PS and likely reflect separate patient populations which differentially respond to environment-based stressors.

Polymorphisms of HLA-DRB1, -DQA1 and -DQB1 in inhabitants of Astana, the capital city of Kazakhstan.

BACKGROUND: Kazakhstan has been inhabited by different populations, such as the Kazakh, Kyrgyz, Uzbek and others. Here we investigate allelic and haplotypic polymorphisms of human leukocyte antigen (HLA) genes at DRB1, DQA1 and DQB1 loci in the Kazakh ethnic group, and their genetic relationship between world populations. METHODOLOGY/PRINCIPAL FINDINGS: A total of 157 unrelated Kazakh ethnic individuals from Astana were genotyped using sequence based typing (SBT-Method) for HLA-DRB1, -DQA1 and -DQB1 loci. Allele frequencies, neighbor-joining method, and multidimensional scaling analysis have been obtained for comparison with other world populations. Statistical analyses were performed using Arlequin v3.11. Applying the software PAST v. 2.17 the resulting genetic distance matrix was used for a multidimensional scaling analysis (MDS). Respectively 37, 17 and 19 alleles were observed at HLA-DRB1, -DQA1 and -DQB1 loci. The most frequent alleles were HLA-DRB1*07:01 (13.1%), HLA-DQA1*03:01 (13.1%) and HLA-DQB1*03:01 (17.6%). In the observed group of Kazakhs DRB1*07:01-DQA1*02:01-DQB1*02:01 (8.0%) was the most common three loci haplotype. DRB1*10:01-DQB1*05:01 showed the strongest linkage disequilibrium. The Kazakh population shows genetic kinship with the Kazakhs from China, Uyghurs, Mongolians, Todzhinians, Tuvinians and as well as with other Siberians and Asians. CONCLUSIONS/SIGNIFICANCE: The HLA-DRB1, -DQA1 and -DQB1 loci are highly polymorphic in the Kazakh population, and this population has the closest relationship with other Asian and Siberian populations.