Smell loss is associated with cognitive impairment in amyotrophic lateral sclerosis patients.

BACKGROUND: Smell loss significantly impacts the quality of life in patients. However, there is limited research on smell loss in individuals with amyotrophic lateral sclerosis (ALS), and the correlation between smell loss and cognitive impairment is unclear. This study aimed to investigate the correlation between smell loss and cognition impairment in ALS patients. METHODS: The study included 216 ALS patients. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and smell identification test specifically for the Chinese population (CSIT) were administered to evaluate participants' cognitive and olfactory function, respectively. RESULTS: After covarying for age, sex, BMI, education level, degree of hunger, dietary bias, eagerness for food, stress, smoking status, alcohol consumption, and upper respiratory tract infection (URTI) or rhinitis, CSIT scores were significantly correlated with ECAS scores (r = 0.162, p = 0.028), especially the ALS-specific scores (r = 0.158, p = 0.031). Even after excluding patients with URTI or rhinitis, the results were similar. CSIT scores were significantly correlated with ECAS scores (r = 0.224, p = 0.011), especially the ALS-specific scores (r = 0.205, p = 0.019). CONCLUSION: In patients with ALS, smell loss is significantly correlated with cognitive impairment, particularly frontotemporal dysfunction. Cognitive dysfunction may lead to worse olfactory performance in ALS patients.

Discovery of an efficacious KDM5B PROTAC degrader GT-653 up-regulating IFN response genes in prostate cancer.

Epigenetic alterations promote cancer development by regulating the expression of various oncogenes and anti-oncogenes. Histone methylation modification represents a pivotal area in epigenetic research and numerous publications have demonstrated that aberrant histone methylation is highly correlated with tumorigenesis and development. As a key histone demethylase, lysine-specific demethylase 5B (KDM5B) demethylates lysine 4 of histone 3 (H3K4) and serves as a transcriptional repressor of certain tumor suppressor genes. Meanwhile, KDM5B inhibits STING-induced intrinsic immune response of tumor cells or recruits SETDB1 through non-enzymatic function to silence reverse transcription elements to promote immune escape. The conventional small molecule inhibitors can only inhibit the enzymatic function of KDM5B with no effect on the non-enzymatic function. In the article, we present the development of the first series of KDM5B degraders based on CPI-455 to inhibit the non-enzymatic function. Among them, GT-653 showed optimal KDM5B degradation efficiency in a ubiquitin proteasome-dependent manner. GT-653 efficiently reduced KDM5B protein levels without affecting KDM5B transcription. Interestingly, GT-653 increased H3K4me3 levels and activated the type-I interferon signaling pathway in 22RV1 cells without significant phenotypic response on cell proliferation.

Surface change of microplastics in aquatic environment and the removal by froth flotation assisted with cationic and anionic surfactants.

Microplastics (MPs) are increasingly released into the environment due to the widespread usage and improper management of plastics. Considerable research efforts have been devoted to the remediation of MPs. Froth flotation has been demonstrated as an effective method to remove MPs in water and sediment. However, there is a lack of knowledge on the regulation of the hydrophobicity/hydrophilicity of MPs surfaces. We found that exposure to the natural environment resulted in the increased hydrophilicity of MPs. The flotation efficiencies of polyvinyl chloride (PVC), polypropylene (PP), polystyrene (PS), and polyethylene glycol terephthalate (PET) MPs decreased to zero after six months of natural incubation in rivers. According to various characterizations, the hydrophilization mechanism is mainly correlated with surface oxidation and the deposition of clay minerals. Inspired by surface wettability conversion, we applied surfactants (collectors) to enhance MPs hydrophobicity and flotation efficiency. Anionic sodium oleate (NaOL) and cationic dodecyl trimethyl ammonium chloride (DTAC) were used to regulate surface hydrophobicity. The effects of collector concentration, pH, conditioning time, and metal ions on MPs flotation were thoroughly elucidated. Characterizations and adsorption experiments were performed to describe the heterogeneous adsorption of surfactants on MPs surfaces. The interaction between surfactants and MPs was explained through density functional theory (DFT) simulations. The dispersion energy between hydrophobic hydrocarbon chains attracts collectors on the MPs surface, and the collector molecules wrap and laminate to MPs surfaces. Flotation using NaOL exhibited a higher removal efficiency, and NaOL was environmentally friendly. Subsequently, we investigated the activation of Ca2+, Fe3+, and Al3+ to further improve the collecting efficiency of NaOL. Under the optimized conditions, MPs in natural rivers could be removed by froth flotation. This study shows the great promise of froth flotation for the application of MPs removal.

A case report of neuronal intranuclear inclusion disease with paroxysmal peripheral neuropathy-like onset lacking typical signs on diffusion-weighted imaging.

Background: Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions and the GGC repeats in the 5'-untranslated region of NOTCH2NLC. The prevalent presence of high-intensity signal along the corticomedullary junction on diffusion-weighted imaging (DWI) helps to recognize this heterogeneous disease despite of highly variable clinical manifestations. However, patients without the typical sign on DWI are often misdiagnosed. Besides, there are no reports of NIID patients presenting with paroxysmal peripheral neuropathy-like onset to date. Case presentation: We present a patient with NIID who suffered recurrent transient numbness in arms for 17 months. Magnetic resonance imaging (MRI) showed diffuse, bilateral white matter lesions without typical subcortical DWI signals. Electrophysiological studies revealed mixed demyelinating and axonal sensorimotor polyneuropathies involving four extremities. After excluding differential diagnosis of peripheral neuropathy through body fluid tests and a sural nerve biopsy, NIID was confirmed by a skin biopsy and the genetic analysis of NOTCH2NLC. Conclusion: This case innovatively demonstrates that NIID could manifest as paroxysmal peripheral neuropathy-like onset, and addresses the electrophysiological characteristics of NIID in depth. We broaden the clinical spectrum of NIID and provide new insights into its differential diagnosis from the perspective of peripheral neuropathy.

Insight into the microplastics release from disposable face mask: Simulated environment and removal strategy.

The fight against the COVID-19 epidemic significantly raises the global demand for personal protective equipment, especially disposable face masks (DFMs). The discarded DFMs may become a potential source of microplastics (MPs), which has attracted much attention. In this work, we identified the detailed source of MPs released from DFMs with laser direct infrared spectroscopy. Polypropylene (PP) and polyurethane (PU) accounted for 24.5% and 57.1% of released MPs, respectively. The melt-blown fabric was a dominant MPs source, however, previous studies underestimated the contribution of mask rope. The captured polyethylene terephthalate (PET), polyamide (PA), polyethylene (PE), and polystyrene (PS) in airborne only shared 18.4% of released MPs. To deepen the understanding of MPs release from medical mask into the aquatic environment, we investigated the effects of environmental factors on MPs release. Based on regression analysis, the effects of temperature, incubation time, and wearing time significantly affect the release of MPs. Besides, acidity, alkalinity, sodium chloride, and humic acid also contributed to the MPs release through corroding, swelling, or repulsion of fibers. Based on the exposure of medical mask to simulated environments, the number of released MPs followed the order: seawater > simulated gut-fluid > freshwater > pure water. Considering the risk of MPs released from DFMs to the environment, we innovatively established a novel flotation removal system combined with cocoamidopropyl betaine, achieving 86% removal efficiency of MPs in water. This work shed the light on the MPs release from DFMs and proposed a removal strategy for the control of MPs pollution.

Stepwise flotation separation of WEEE plastics by polymeric aluminum chloride towards source control of microplastics.

The mismanagement of waste electrical and electronic equipment (WEEE) resulted in numerous discarded plastics in the natural environment, and these waste plastics might experience aging, breaking, and migration, which becomes a crucial microplastic source. Sustainable management of WEEE plastics presents a considerable opportunity for resource recovery and microplastic pollution prevention. Flotation separation is a significant process of mechanical recycling, while most flotation methods can only deal with binary plastic mixtures. In this work, an advanced, stepwise, and sustainable flotation method was advocated to separate multi-plastics by polymeric aluminum chloride (PAC) modification. The abundant hydrophilic groups and environmental friendliness of PAC prompted us to further investigate the wetting effect. PAC had varied hydrophilization effects on acrylonitrile butadiene styrene (ABS) and polystyrene (PS) surfaces, but polyethylene terephthalate (PET) retained hydrophobicity. Treatment conditions, including PAC dosage, temperature, time, and pH were optimized. 100% of PET could be purified after primary separation, and the purities of ABS and PS could reach 100% and 97.4% after secondary separation, respectively. The strength of the interaction was determined by the different surface potentials and functional groups. In PAC solution, long-chain molecules or ions might interact with plastic surfaces electrostatically, and Al3+ could bridge long-chain molecules and plastic surfaces, thereby strengthening the polymer hydrophilicity. We further improved the PAC treatment process, and the reuse of PAC reduced modifier usage to 84.4 g/ton waste plastics, which was cost-effective in industrial applications. A preliminary evaluation of the energy consumption and environmental impact indicated that PAC treatment was superior to other modification methods. This work is an initial attempt at the stepwise separation of waste plastic and shows promising prospects for recycling plastic waste.

A clean and efficient flotation towards recovery of hazardous polyvinyl chloride and polycarbonate microplastics through selective aluminum coating: Process, mechanism, and optimization.

Polyvinyl chloride (PVC) and polycarbonate (PC) microplastics are major sources of hazardous chlorine and bisphenol A, threatening the ecosystem and environment. Plastic recycling can control the source of microplastics pollution, but the recycling of PVC and PC will be prevented by invalid separation. We established a novel and clean flotation method to separate PVC and PC microplastics by using aluminum coating. Trace amounts of Al(OH)3 can selectively coat the PVC microplastics surface due to its strong affinity for PVC. The contact angle of PVC decreases by 24° due to abundant hydroxyl groups of Al(OH)3 coating, whereas PC remained hydrophobic. Response surface methodology (RSM) combining Box-Behnken design (BBD) is used to optimize modification. A quadratic model is established to predict PC purity, explore the interaction between pH, aluminum chloride concentration, and ultrasonic duration. The recovery and purity of microplastics can exceed 99.65% with parameter optimization. The effects of multi-component, brand, shape, size, and mass ratio of plastics are utilized to evaluate the application potential. The suitable situations and limits of this method are disclosed. The aluminum coating offers significant benefits over other modifications in terms of reaction temperature, treatment time, and pollution prevention. Flotation based on aluminum coating provides a new insight for separating and recycling microplastics.

Collagen VI-related myopathy with scoliosis alone: A case report and literature review.

BACKGROUND: Scoliosis is a complex three-dimensional deformity of spine and one of the common complications of collagen VI-related myopathy, caused by mutations in collagen type VI alpha 1 chain (COL6A1), COL6A2, and COL6A3 genes. The typical clinical presentations of collagen VI-related myopathy include weakness, hypotonia, laxity of distal joints, contractures of proximal joints, and skeletal deformities. CASE SUMMARY: A 28-year-old female presented with scoliosis for 28 years without weakness, hypotonia, laxity of distal joints, and contracture of proximal joints. Computed tomography and magnetic resonance imaging revealed hemivertebra, butterfly vertebra, and the missing vertebral space. Patients underwent orthopedic surgery and paravertebral muscle biopsy. The Cobb angle dropped from 103.4° to 52.9°. However, the muscle biopsy showed neurogenic muscular atrophy with myogenic lesions, suggesting congenital muscular dystrophy. Gene analysis indicated that mutations in COL6A1 (c.1612-10G>A) and COL6A2 (c.115+10G>T, c.2749G>A). Immunohistochemistry staining for collagen VI displayed shallow and discontinuous. Eventually, the patient was diagnosed as collagen VI-related myopathy. CONCLUSION: This newly found subtype of collagen VI-related myopathy has no typical manifestations; however, it is characterized by severe scoliosis and congenital vertebral deformity.

Hydrophilic modification of polycarbonate surface with surface alkoxylation pretreatment for efficient separation of polycarbonate and polystyrene by froth flotation.

Waste polystyrene (PS) and polycarbonate (PC) are crucial components arising from mixtures of plastic products, whose recycling is significantly limited by separation efficiency. In this work, to assist the flotation separation of PC and PS, we proposed a novel modification technology of surface alkoxylation pretreatment (SAP) where PC surface reacted with glycerol and urea. The SAP could selectively transform the hydrophobic PC into hydrophilic plastic, while the PS remained its hydrophobic surface owing to the exclusion from SAP process. Benefiting from the hydrophilic PC, the separation efficiency of PS and PC could reach the maximum of 99.34% under optimum conditions (urea dosage of 5 g, pretreatment temperature of 130 °C, pretreatment time of 10 min, flotation time of 2.5 min, frother concentration of 16.5 mg/L, and airflow rate of 7.2 mL/min). The mechanism of SAP was systematically analyzed by wettability, surface morphology, molecular weight, and chemical reactions. Compared with PS plastic, the pretreated PC presented better wettability, rougher surface, and significantly reducing molecular weight. The improvement of PC hydrophilicity can be attributed to the cleavage of ester bonds on backbone chains and the introduction of hydrophilic hydroxyl groups. The effective SAP process proves that chemical recycling of waste plastic can provide a novel strategy for surface modification and flotation separation of PS and PC.

Flotation separation of polyethylene terephthalate from waste packaging plastics through ethylene glycol pretreatment assisted by sonication.

The recycling of packaging plastics is hindered by the various plastic mixtures and their similar surface properties. Plastic separation is a key step to improve recycling efficiency of waste plastics. We proposed a simple and efficient protocol to separate polyethylene terephthalate (PET) from polycarbonate (PC), acrylonitrile-butadienestyrene copolymer (ABS), and polyvinyl chloride (PVC) by converting PET surface from hydrophobicity to hydrophilicity. PET surface was modified by potassiumhydroxide (KOH)and ethylene glycol ((CH2OH)2) with the aid of sonication. Contact angle, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were used to research the reactions on PET surface. It can be confirmed that the reaction of base-catalyzed transesterification occurs, leading to a hydrophilic PET plastic. We investigated the effects of ultrasonic power, ultrasonic time, (CH2OH)2 dosage, KOH dosage, flotation time, and frother concentration on the flotation separation. The flotation recovery and purity of PET are 98.8% and 100%, respectively when (CH2OH)2 dosage is 10 mL, KOH dosage is 2 g, ultrasonic time is 5 min, ultrasonic intensity is 160 W, flotation time is 4 min, and frother concentration is 52.7 mg/L. This study provided a novel surface modification with reliable mechanisms for the flotation of PET from plastic mixtures.

Separation of polyvinylchloride and acrylonitrile-butadiene-styrene combining advanced oxidation by S2O82-/Fe2+ system and flotation.

A combining technology of advanced oxidation by S2O82-/Fe2+ system and flotation was proposed for separating polyvinyl chloride (PVC) and acrylonitrile butadiene styrene (ABS). In this research, sodium persulfate was activated by heating and ferrous ions. The separation efficiency of PVC/ABS oxidized by S2O82-/Fe2+ was higher than that by sodium persulfate. The mechanism of this process was investigated through contact angle, Fourier transform infrared spectroscopy (FT-IR) inductively coupled plasma (ICP), nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS). The floatability of ABS reduced owing to the introduction of oxygen-containing functional groups such as carbonyl (OCO) and hydroxyl (OH), which was a result of oxidation by sulfate radicals (SO4·-). The optimal conditions for separating PVC and ABS were: Na2S2O8 concentration 0.1 M, molar ratio (S2O82-/Fe2+) 200, treatment time 10 min, flotation time 4 min, frother concentration 14.7 mg L-1 and airflow rate 6.8 mL min-1. Novel kinetics of pretreatment time and flotation were proposed and researched in this work. The max rate constant of PVC/ABS flotation was 0.64 min-1. In addition, the pretreatment solution can be reused for three times with superior performance. The recovery and purity of PVC reached 100% and 99.7%, respectively. According to reasonable evaluation, the combination of S2O82-/Fe2+ advanced oxidation and flotation is a practical and efficient technology for separating PVC and ABS.

[Clinical and electrophysiological characteristics and therapeutic analysis of 9 patients with Lewis-Sumner syndrome].

OBJECTIVE: To investigate the clinical characteristics, electrophysiological findings and treatment response of Lewis-Sumner syndrome (LSS). METHODS: Data of nine patients with LSS, who were diagnosed and treated from May 2008 to August 2014 in Department of Neurology, Peking University Third Hospital, were analyzed retrospectively, including clinical features, electrophysiological studies, pathological characteristics, therapy and follow up. RESULTS: The nine cases included seven males and two females, with the average age being 29 years old (18-64 years old). The follow-ups after treatment were between 6 months to 48 months. All 9 cases were asymmetrical onset, and the distal part of limbs was initially affected in 8 cases. Five cases presented with the initial symptom of sensorimotor, 3 cases with purely motor and only 1 case with sensory. The disease developed two forms: multifocal distribution and symmetrical distribution. Electrophysiological studies demonstrated conduction blocks on non-entrapment sites, involving mainly median nerve and ulnar nerve. Sural nerve biopsy presented mild demyelination without inflammatory infiltration. The symptoms of patients had some degrees of improvement after immunotherapy, and the prognosis was favorable. CONCLUSIONS: Lewis-Sumner syndrome presents the initial symptoms of asymmetrical sensorimotor neuropathy mostly affecting the upper extremities. Median nerve and ulnar nerve are the most common involvements. Electrophysiological studies demonstrate motor nerve conduction block. The major finding of pathology is mild demyelinated. The patients have a positive response to immunotherapy.

[The clinical pathological characteristics and follow-up of 4 cases of immune-mediated necrotizing myopathy].

OBJECTIVE: To characterize the clinical, electrophysiology and neuropathological features of 4 cases with immune-mediated necrotizing myopathy (IMNM). METHODS: We retrospectively analyzed the clinical, electrophysiology, neuropathological characteristics of 4 IMNM patients with muscular and skin biopsy in our department during 4 years (from January 2011 to January 2014). RESULTS: Among these 4 patients, 2 were men and 2 were women (aged 37 to 58 years) with disease duration ranging from 1 month to 60 months. Two patients were with acute onset and 2 with chronic onset. All 4 patients had proximal muscle weakness with three patients with cervical flexor muscle weakness and one with respiratory muscles weakness and noninvasive ventilator assisted respiration. One patient had interstitial lung disease. The anti-signal recognition particle antibodies were strong positive in all 4 patients. Muscle biopsy showed group necrotizing and regenerating fibers in one patient and few scattered necrotizing and regenerating fibers in the other 3 patients. Both muscle fiber hypertrophy and muscle fiber atrophy together with proliferation of connective tissue on endomysium could be viewed in all 4 patients. However, very few inflammatory cells were detectable in patients. One patient was treated with corticosteroids and the other three were treated with combination of corticosteroids and immunosuppressant drugs. CONCLUSIONS: IMNM is characterized by heterogeneity at disease onset, severity and iInvolvement of muscles with, however, similary pathological changes including the presence of numerous necrotic and regenerating fibers with little or none inflammation. Corticosteroid and/or immunosuppressant is effective for patients.

Nerve biopsy findings contribute to diagnosis of multiple mononeuropathy: 78% of findings support clinical diagnosis.

Multiple mononeuropathy is an unusual form of peripheral neuropathy involving two or more nerve trunks. It is a syndrome with many different causes. We reviewed the clinical, electrophysiological and nerve biopsy findings of 14 patients who suffered from multiple mononeuropathy in our clinic between January 2009 and June 2013. Patients were diagnosed with vasculitic neuropathy (n = 6), perineuritis (n = 2), chronic inflammatory demyelinating polyradiculoneuropathy (n = 2) or Lewis-Sumner syndrome (n = 1) on the basis of clinical features, laboratory data, electrophysiological investigations and nerve biopsies. Two patients who were clinically diagnosed with vasculitic neuropathy and one patient who was clinically diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy were not confirmed by nerve biopsy. Nerve biopsies confirmed clinical diagnosis in 78.6% of the patients (11/14). Nerve biopsy pathological diagnosis is crucial to the etiological diagnosis of multiple mononeuropathy.

[The clinical electrophysiology and pathological characteristics of 15 cases of vasculitic neuropathy].

OBJECTIVE: To summarize the clinical features, electrophysiology and neuropathological characteristics of peripheral nerves in patients with vasculitic neuropathy. METHODS: We retrospectively analyzed the clinical, electrophysiology and neuropathological characteristics of 15 patients with vasculitic neuropathy who underwent electrophysiology and sural nerve biopsy in our department from January 2009 to June 2013. RESULTS: There were 8 males and 7 females, aged from 38 to 82 years old, with a peripheral neuropathy course ranged from 0.5 month to 60 months. In the total of 15 patients, 3 patients were diagnosed as nonsystemic vasculitic neuropathy, while the other 12 patients were diagnosed as systemic vasculitis neuropathy (SVN) including 5 cases of primary systemic vasculitis and 7 cases of secondary systemic vasculitis. In patients diagnosed as primary systemic vasculitis, there were 2 cases of Churg-Strass syndrome (CSS) and 3 cases of ANCA associated vasculitis. In patients diagnosed as secondary systemic vasculitis, there were 1 case of systemic lupus erythematosus (SLE), 2 cases of sicca syndrome (SS), 3 cases of rheumatoid arthritis (RA), 1 case of Behcet' s disease associated with thyroid papillary carcinoma, 1 case of hepatitis B and 1 case of RA-associated SS. For the pathological features of vasculitic neuropathy, type 1 lesion was found in 4 patients, type 2 lesion in 2 patients, and type 3 lesion in 9 patients. Axon degeneration was observed in 8 patients, while 7 patients manifested as axon degeneration associated with demyelination and local thickening of the perineurium was found in 2 patients. CONCLUSION: Multiple mononeuropathy and asymmetric polyneuropathy are the common clinical presentations of vasculitic neuropathy. Electrodiagnostic testing almost always reveals the evidence of a predominantly axonal and sensorimotor process with associated demyelination presented in some cases. Sural nerve biopsy shows changes indicative of an axonopathy.

Intraneural perineurioma affecting multiple nerves: a case report and literature review.

Intraneural perineurioma is a neoplasm of perineurial cells, corresponding to WHO grade I. We present a case of intraneural perineurioma affecting multiple nerves, which usually involved one or two of major nerve trunks in one patient. We describe the clinical presentation, magnetic resonance (MR) neurography characteristics, and pathological characteristics. The differential diagnosis with other diseases, such as neurofibroma, Schwannomatosis and HNPP, will also be discussed. We also review the literature in efforts to highlight recent studies on intraneural perineurioma and heighten and awareness for the possible presentations of this disorder.

[Clinico-electrophysiological and pathological characteristics of neuropathy in Sjögren's syndrome: a report of 5 cases].

OBJECTIVE: To summarize the clinical features, electrophysiological and neuropathological characteristics of peripheral nerves in patients with primary Sjögren's syndrome (SS). METHODS: We retrospectively analyzed the clinical, electrophysiological and neuropathological characteristics of 5 female SS patients with neuropathy complications undergoing electrophysiology and sural nerve biopsy at our department from January 2011 to June 2013. RESULTS: They had an age range of 20-75 years. The course of peripheral neuropathy ranged 0.5-60 months and the whole course 12-240 months. pSS-associated neuropathy included multiple mononeuropathy (n = 1), symmetrical axonal sensorimotor polyneuropathy (n = 1) and sensory ganglioneuronopathy (n = 3). All biopsies showed varying degrees of myelinated fiber loss. Three biopsies had axonal degeneration associated with demyelination. However, there was no formation of onion bulb regeneration or plexus. Necrotizing vasculitis was diagnosed in 2 cases. CONCLUSION: The manifestations of peripheral nerve n pSS include multiple mononeuropathy, axonal symmetric sensorimotor polyneuropathy and sensory gangioneuronopathy. Sural biopsy shows typical necrotizing vasculitis in some cases and myelinated fiber loss and axonal degeneration in others. The pathogenic mechanisms of neurological involvement in pSS remain unknown. However, vasculitis, ischemic and immunological insults resulting in sensory gangioneuronopathy have been described.

Association of polymorphisms in vascular endothelial growth factor gene with the age of onset of amyotrophic lateral sclerosis.

This study investigated the association between polymorphisms in vascular endothelial growth factor (VEGF) gene (-1558C-T, -1190A-G and -1154A-G) and age at onset of amyotrophic lateral sclerosis (ALS). Between July 2000 and June 2004 we conducted a clinical genetic study at Peking University Third Hospital, China. The analyses included a total of 93 ALS patients. Genotyping was performed by using the 5'-nuclease assay technology (Applied Biosystems) with TaqMan allele-specific fluorogenic oligonucleotide probes. We used multivariate linear regression modelling and haplotype-based association test to analyse the association of VEGF gene polymorphisms with the age of onset, adjusting for initial symptoms and sex. The results indicated that patients with the -1190A/G and -1190G/G genotypes exhibited about a 4.1- and 9.4-years earlier onset of ALS than the patients with the -1190A/A genotype. A similar pattern emerged when the VEGF -1154A-G gene was considered: the beta was -7.9(p<0.001) years and -11.7(p<0.001) years for -1154A/G and -1154G/G genotypes, respectively. The VEGF -1558C-T had a positive effect in the -1558C/T group (p = 0.007, beta = 7.0) and -1558T/T (p<0.001, beta = 9.6) compared to the -1558C/C group. We neither observed an interaction nor haplotype association with age onset among -1558C-T, -1190A-G and -1154A-G. In conclusion, our results indicate, for the first time, that there was an important association between the polymorphism of the VEGF gene and age of ALS onset. This suggests a possible role for VEGF variability in the aetiology of individual differences in ALS onset.

VEGF C2578A polymorphism does not contribute to amyotrophic lateral sclerosis susceptibility in sporadic Chinese patients.

A linkage and association of the VEGF (vascular endothelial growth factor) C2578A polymorphism and amyotrophic lateral sclerosis (ALS) has been found in some studies. We analysed the C2578A polymorphism in sporadic ALS patients from a Chinese population. The polymorphism was analysed in 115 patients and 200 healthy individuals by amplifying across position 2705 to 2494 of the promoter region of the VEGF gene. It was found that the frequency of the allele A was 24% in ALS patients and 28% in healthy individuals (p = 0.264). Comparing the background of this polymorphism in healthy individuals between Chinese and Caucasians, significant decreases were found in the frequencies of the A/A genotype and allele A (p(s)<0.001). We concluded that VEGF C2578A polymorphism did not confer a susceptibility to sporadic Chinese ALS patients, which was in disagreement with that reported previously in Caucasian populations and might be ascribed to the different genetic background between Chinese and Caucasians.