Association of follicle-stimulating hormone receptor single nucleotide polymorphisms with fertility in Greek men.

BACKGROUND AND OBJECTIVE: Although several epidemiological studies have been conducted, the impact of follicle-stimulating hormone receptor (FSHR) polymorphisms on male infertility remains unclear. The aim of this study was to investigate the prevalence of specific FSHR single nucleotide polymorphisms (SNPs) in the Greek population and associate the latter with the clinical phenotype. PATIENTS AND METHODS: We enrolled 96 subjects: men with idiopathic non-obstructive azoospermia (n = 78) were compared with a control group of fertile men (n = 18) for SNPs in FSHR positions c.-29, c.566, c.919, and c.2039. The SNP in position 566 (c.566C > T) was assessed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and the other three SNPs (c.-29G > A, c.919A > G, c.2039A > G) with single-strand conformation polymorphism (SSCP); all of them were validated with DNA sequence. RESULTS: No polymorphisms were detected in positions c.-29 and c.919 (c.-29G > A, c.919A > G). The heterozygous SNP (AG) at position 2039 was associated with different size of the right testis (p = 0.008). There was no association between the c.566C > T SNPs polymorphism and hormonal or semen parameters. The combination SNP 2039 AA with 566 CT revealed significant association with FSH and LH concentrations. CONCLUSIONS: FSHR SNPs at positions c.-29, c.566, c.919, and c.2039 (c.-29G > A, c.566C > T, c.919A > G, c.2039A > G) do not appear to play specific roles in male infertility. Larger studies are needed to confirm these results.

Modeling of signaling pathways in chondrocytes based on phosphoproteomic and cytokine release data.

OBJECTIVE: Chondrocyte signaling is widely identified as a key component in cartilage homeostasis. Dysregulations of the signaling processes in chondrocytes often result in degenerative diseases of the tissue. Traditionally, the literature has focused on the study of major players in chondrocyte signaling, but without considering the cross-talks between them. In this paper, we systematically interrogate the signal transduction pathways in chondrocytes, on both the phosphoproteomic and cytokine release levels. METHODS: The signaling pathways downstream 78 receptors of interest are interrogated. On the phosphoproteomic level, 17 key phosphoproteins are measured upon stimulation with single treatments of 78 ligands. On the cytokine release level, 55 cytokines are measured in the supernatant upon stimulation with the same treatments. Using an Integer Linear Programming (ILP) formulation, the proteomic data is combined with a priori knowledge of proteins' connectivity to construct a mechanistic model, predictive of signal transduction in chondrocytes. RESULTS: We were able to validate previous findings regarding major players of cartilage homeostasis and inflammation (e.g., IL1B, TNF, EGF, TGFA, INS, IGF1 and IL6). Moreover, we studied pro-inflammatory mediators (IL1B and TNF) together with pro-growth signals for investigating their role in chondrocytes hypertrophy and highlighted the role of underreported players such as Inhibin beta A (INHBA), Defensin beta 1 (DEFB1), CXCL1 and Flagellin, and uncovered the way they cross-react in the phosphoproteomic level. CONCLUSIONS: The analysis presented herein, leveraged high throughput proteomic data via an ILP formulation to gain new insight into chondrocytes signaling and the pathophysiology of degenerative diseases in articular cartilage.

The role of reelin gene polymorphisms in the pathogenesis of Alzheimer's disease in a Greek population.

Reelin is an extracellular signaling glycoprotein, which plays a significant role in cytoarchitectonic pattern formation of different brain areas during development. Reelin gene is located on chromosome 7q22. The aim of this study is to investigate the possible association of the following reelin polymorphisms SNP Intron12A/C (rs727531), SNP Exon15A/G (rs2072403), SNP Intron15G/T (rs2072402), SNP Exon22c/g (rs362691), SNP Intron41G/T (rs362719) and SNP Intron59C/T (rs736707) in the pathogenesis of Alzheimer 's disease and the frequency of these polymorphisms in the population of Northern Greece. The study included two groups, A and B. Group A consisted of 50 patients with Alzheimer 's disease and group B of 70 healthy controls. Genomic DNA isolated from blood was used for PCR and subsequent RFLP analysis. According to our results, the exon 22 C/G marker of Reelin is significantly associated with Alzheimer 's disease in the Greek population but the Likelihood Ratio Test shows that the GT haplotype ++ this polymorphism does not affect the phenotype of group A in relation to Group B. This is the first report on a Greek population-based approach.