Biochemical and neuropathological findings in a Creutzfeldt-Jakob Disease patient with the rare Val180Ile-129Val haplotype in the prion protein gene

Genetic Creutzfeldt-Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (PRNP) in phase with residue 129M is the most frequent cause of gCJD in East Asia, whereas it is quite uncommon in Caucasians. We report on a gCJD patient with the rare V180I-129V haplotype, showing an unusually long duration of the disease and a characteristic pathological PrP (PrPSc) glycotype. Family members carrying the mutation were fully asymptomatic, as commonly observed with this mutation. Neuropathological examination showed a lesion pattern corresponding to that commonly reported in Japanese V180I cases with vacuolization and gliosis of the cerebral cortexes, olfactory areas, hippocampus and amygdala. PrP was deposited with a punctate, synaptic-like pattern in the cerebral cortex, amygdala and olfactory tract. Western blot analyses of proteinase-K-resistant PrP showed the characteristic two-banding pattern of V180I gCJD, composed of mono- and un-glycosylated isoforms. In line with reports on other V180I cases in the literature, Real-Time Quaking Induced Conversion (RT-QuIC) analyses did not demonstrate the presence of seeding activity in the cerebrospinal fluid and olfactory mucosa, suggesting that this haplotype also may result in a reduced seeding efficiency of the pathological PrP. Further studies are required to understand the origin, penetrance, disease phenotype and transmissibility of 180I-129V haplotype in Caucasians

Increased FGF23 serum level is associated with unstable carotid plaque in type 2 diabetic subjects with internal carotid stenosis.

BACKGROUND: The object of this study was to investigate the potential role of FGF23 on plaque stability in type 2 diabetic patients with internal carotid artery stenosis. METHODS: In this retrospective observational study, we analyzed FGF23 serum level in 361 type 2 diabetic patients with internal carotid artery stenosis undergoing carotid endarterectomy and in 598 diabetic controls without carotid atherosclerosis. RESULTS: We found that FGF23 median serum levels was significantly higher in patients than in diabetic controls [67.7 (59.5-77.8) pg/mL and 43.89 (37.5-50.4), P < 0.001] and was significantly and independently associated with unstable plaque in patients with internal carotid artery stenosis [OR, 5,71 (95% CI, 2.09-15.29]. CONCLUSIONS: We have found, for the first time, that FGF23 could be associated with unstable plaque in type 2 diabetic patients with internal carotid artery stenosis

RANK/RANKL/OPG pathway: genetic association with history of ischemic stroke in Italian population

OBJECTIVE: RANKL is a member of the TNF superfamily that stimulates chemokine release, monocyte/macrophage matrix migration and matrix metalloproteinase activity and plays an important role in atherosclerosis. In our study, we have evaluated whether RANKL gene polymorphisms are involved in ischemic stroke in Italian subjects. PATIENTS AND METHODS: In a retrospective study we have included 487 patients (242 males, 245 females) with history of ischemic stroke and 543 control subjects without history of ischemic stroke (277 males, 276 females). The rs9533156, and rs2277438 gene polymorphisms of the RANKL gene were analyzed by PCR and restriction fragment length polymorphism. RESULTS: We found that the rs9533156 gene polymorphism of the RANKL gene was significantly (55.0% versus 36.5%, p &lt; 0.0001) and independently (adjusted OR 6.28 [2.34-4.21]) associated with history of ischemic stroke. No statistically significant difference was found between the two groups in our population for the rs2277438 gene polymorphism (p = 439). Furthermore, we have confirmed that rs 3134069, rs 2073617 and rs 2073618 polymorphisms of the OPG gene were significantly and independently associated with cerebrovascular disorders. CONCLUSIONS: The present study identifyes, for the first time, the genetic variant of RANKL as an independent risk factor for ischemic stroke

Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients.

Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. The present study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved in ischemic stroke in an Italian population with diabetes. Participants in a retrospective case-control study included 364 diabetic patients (180 males, 184 females) with history of ischemic stroke and 492 diabetic subjects without history of ischemic stroke (252 males, 240 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism. We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (34.1 vs. 9.5 %, P < 0.0001; 30.8 vs. 6.3 %, P < 0.0001 and 26.4 vs. 11.6 % P < 0.0001, respectively) and independently (adjusted OR 5.15 [3.46-7.68], OR 6.63 [4.26-10.31], and OR 3.03 [2.04-4.50], respectively) associated with history of ischemic stroke. We also found that these three polymorphisms act synergistically in patients with stroke history. The TNFRSF11B gene polymorphisms studied are associated with history of ischemic stroke and synergistic effects between these genotypes might be potential markers for cerebrovascular disorders