Cytomegalovirus seropositivity correlates with both human ß-defensin 1 and IFN-γ downregulation in women with obesity.

Human ß-defensin 1 (hBD-1) is a constitutively expressed antimicrobial peptide with antiviral properties. CMV seropositivity has been associated with obesity. It is unknown if hBD-1 levels of are altered in women with obesity and/or CMV seropositivity. In a pilot project of 31 adult women with CMV seropositivity, we calculated the correlation among hBD-1 serum levels (ELISA) and IgG anti-CMV-Index with anthropometric measurements, lipid profiles and glucose levels. hBD-1 showed negative correlation with triglycerides (TG) (r = -0.617; p = 0.033,) and hip circumference (r = -0.596; p = 0.041,). IgG anti-CMV index was negatively correlated with hBD-1 levels and positively correlated with TG (r = 0.702; p = 0.011,) and HC (r = 0.583; p = 0.047,) in women with obesity. As expected, hBD-1 levels correlates with IFN-γ (an antimicrobial peptide elicitor) in the three analyzed groups.These results shows that CMV seropositivity correlates with both IFN-γ levels and hBD-1 levels which in contrast with non-CMV seropositivity scenario, is commonly found an IFN-γ upregulation in individuals with obesity. Further research is encouraged to test if CMV is causing the observed downregulation of the antiviral immune responses of both hBD-1 and IFN-γ as well as their involved mechanisms.

Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis.

Even though a mutation in monogenic diseases leads to a "classic" manifestation, many disorders exhibit great clinical variability that could be due to modifying genes also called minor genes. Fabry disease (FD) is an X-linked inborn error resulting from the deficient or absent activity of alpha-galactosidase A (α-GAL) enzyme, that leads to deposits of globotriaosylceramide. With our proprietary software SNPclinic v.1.0, we analyzed 110 single nucleotide polymorphisms (SNPs) in the proximal promoter of 14 genes that could modify the FD phenotype FD. We found seven regulatory-SNP (rSNPs) in three genes (IL10, TGFB1 and EDN1) in five cell lines relevant to FD (Cardiac myocytes and fibroblasts, Astrocytes-cerebellar, endothelial cells and T helper cells 1-TH1). Each SNP was confirmed as a true rSNP in public eQTL databases, and additional software suggested the prediction of variants. The two proposed rSNPs in IL10, could explain components for the regulation of active B cells that influence the fibrosis process. The three predicted rSNPs in TGFB1, could act in apoptosis-autophagy regulation. The two putative rSNPs in EDN1, putatively regulate chronic inflammation. The seven rSNPs described here could act to modulate Fabry's clinical phenotype so we propose that IL10, TGFB1 and EDN1 be considered minor genes in FD.

Predicted regulatory SNPs reveal potential drug targets and novel companion diagnostics in psoriasis.

Psoriasis is an autoimmune disease associated with interleukins, their receptors, key transcription factors and more recently, antimicrobial peptides (AMPs). Cathelicidin LL-37 is an AMP proposed to play a fundamental role in psoriasis etiology. With our proprietary software SNPClinic v.1.0, we analyzed 203 common SNPs (MAF frequency â€‹> â€‹1%) in proximal promoters of 22 genes associated with psoriasis. These include nine genes which protein products are classic drug targets for psoriasis (TNF, IL17A, IL17B, IL17C, IL17F, IL17RA, IL12A, IL12B and IL23A). SNPClinic predictions were run with DNAseI-HUP chromatin accessibility data in eight psoriasis/epithelia-relevant cell lines from ENCODE including keratinocytes (NHEK), TH1 and TH17 lymphocytes. Results were ranked quantitatively by transcriptional relevance according to our novel Functional Impact Factor (FIF) parameter. We found six rSNPs in five genes (CAMP/cathelicidin, S100A7/psoriasin, IL17C, IL17RA and TNF) and each was confirmed as true rSNP in at least one public eQTL database including GTEx portal and ENCODE (Phase 3). Predicted regulatory SNPs in cathelicidin, IL17C and IL17RA genes may explain hyperproliferation of keratinocytes. Predicted rSNPs in psoriasin, IL17C and cathelicidin may contribute to activation and polarization of lymphocytes. Predicted rSNPs in TNF gene are concordant with the epithelium-mesenchymal transition. In spite that these results must be validated in vitro and in vivo with a functional genomics approach, we propose FOXP2, RUNX2, NR2F1, ELF1 and HESX1 transcription factors (those with the highest FIF on each gene) as novel drug targets for psoriasis. Furthermore, four out of six rSNPs uncovered by SNPClinic v.1.0 software, could also be validated in the clinic as companion diagnostics/pharmacogenetics assays for psoriasis prescribed drugs that block TNF-α (e.g. Etanercept), IL-17 (e.g. Secukinumab) and IL-17 receptor (Brodalumab).

Generalized hypertrichosis syndromes in Mexico.

Hypertrichosis is a rare condition characterized by excessive hair in areas of the body that are not predominantly androgen dependent. We can identify three main syndromes with congenital generalized hypertrichosis terminalis described in Mexico. The first is X-linked generalized hypertrichosis, an ultra-rare disease, with few cases reported to date. The second is Cantú syndrome, also known as hypertrichotic osteochondrodysplasia, which has a wide spectrum of clinical manifestations and is caused by pathogenic variants in ABCC9 and KCNJ8. The third is congenital hypertrichosis terminalis with or without gingival hyperplasia, which displays other features and involves several associated genes. The first two syndromes were described by the Mexican geneticist José María Cantú, and the concept of atavistic genes was invoked to explain the emergence of this outstanding trait. By understanding the genetic and pathophysiological basis of hypertrichosis, we can offer effective treatment to patients and help solve esthetic problems related to hair growth.