Qiang Gang - Academia.edu (original) (raw)

Papers by Qiang Gang

Genetic advances in sporadic inclusion body myositis

Current opinion in rheumatology, 2015

To describe recent developments in the genetics of sporadic inclusion body myositis (sIBM). Genes... more To describe recent developments in the genetics of sporadic inclusion body myositis (sIBM). Genes located within major histocompatibility complex regions remain the strongest genetic association with sIBM. The rs10527454 polymorphism in the TOMM40 gene seems to have a disease modifying effect on sIBM by delaying the onset of symptoms, and this effect may be enhanced by the APOE ε3/ε3 genotype. Rare variants in the VCP and SQSTM1 genes have been identified in sIBM patients in two studies using targeted next-generation sequencing and whole-exome sequencing. Two studies have confirmed the correlation between the amount of cytochrome c oxidase -deficient fibres and the proportion of mitochondrial DNA (mtDNA) deletions in sIBM. Some rare variants in mtDNA-related nuclear genes have also been reported. There have been advances in the genetics of sIBM over the past 2 years facilitated by the use of next-generation sequencing. Genes that cause hereditary IBM, which has clinical or pathologi...

Neurology, Jan 21, 2015

We performed a systematic review and meta-analysis to assess whether the presence of cerebral mic... more We performed a systematic review and meta-analysis to assess whether the presence of cerebral microbleeds (CMBs) on pretreatment MRI scans of patients with acute ischemic stroke treated with thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (ICH). We searched PubMed for relevant studies and calculated pooled odds ratios (ORs) for symptomatic ICH, using the Mantel-Haenszel fixed-effects method, among individuals with vs without CMBs on pretreatment MRI scans. To minimize potential bias, sensitivity analysis was performed including studies providing data on patients treated only with IV thrombolysis. Ten eligible studies including 2,028 patients were pooled in meta-analysis. The overall prevalence of CMBs was 23.3%. Among patients with CMBs, 40 of 472 (8.5%; 95% confidence interval [CI]: 6.1%-11.4%) experienced a symptomatic ICH after thrombolysis compared with 61 of 1,556 patients (3.9%; 95% CI: 3%-5%) without CMBs. The pooled OR of ICH across ...

Orphanet J Rare Dis, 2014

Sporadic inclusion body myositis (sIBM) is the commonest idiopathic inflammatory muscle disease i... more Sporadic inclusion body myositis (sIBM) is the commonest idiopathic inflammatory muscle disease in people over 50 years old. It is characterized by slowly progressive muscle weakness and atrophy, with typical pathological changes of inflammation, degeneration and mitochondrial abnormality in affected muscle fibres. The cause(s) of sIBM are still unknown, but are considered complex, with the contribution of multiple factors such as environmental triggers, aging and genetic susceptibility. This review summarizes the current understanding of the genetic contributions to sIBM and provides some insights for future research in this mysterious disease with the advantage of the rapid development of advanced genetic technology. An international sIBM genetic study is ongoing and whole-exome sequencing will be applied in a large cohort of sIBM patients with the aim of unravelling important genetic risk factors for sIBM.

Current Rheumatology Reports, 2014

Sporadic inclusion body myositis (IBM) is an acquired muscle disorder associated with ageing, for... more Sporadic inclusion body myositis (IBM) is an acquired muscle disorder associated with ageing, for which there is no effective treatment. Ongoing developments include: genetic studies that may provide insights regarding the pathogenesis of IBM, improved histopathological markers, the description of a new IBM autoantibody, scrutiny of the diagnostic utility of clinical features and biomarkers, the refinement of diagnostic criteria, the emerging use of MRI as a diagnostic and monitoring tool, and new pathogenic insights that have led to novel therapeutic approaches being trialled for IBM, including treatments with the objective of restoring protein homeostasis and myostatin blockers. The effect of exercise in IBM continues to be investigated. However, despite these ongoing developments, the aetiopathogenesis of IBM remains uncertain. A translational and multidisciplinary collaborative approach is critical to improve the diagnosis, treatment, and care of patients with IBM.

Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum

Journal of Neurology, Neurosurgery & Psychiatry, 2012

Sporadic cerebral amyloid angiopathy (CAA) is a common age related cerebral small vessel disease,... more Sporadic cerebral amyloid angiopathy (CAA) is a common age related cerebral small vessel disease, characterised by progressive deposition of amyloid-β (Aβ) in the wall of small to medium sized arteries, arterioles and capillaries of the cerebral cortex and overlying leptomeninges. Previously considered to be a rare neurological curiosity, CAA is now recognised as an important cause of spontaneous intracerebral haemorrhage and cognitive impairment in the elderly, two fundamental challenges in the field of cerebrovascular disease. Our understanding of the pathophysiology and clinical manifestations of CAA continues to evolve rapidly, with the use of transgenic mouse models and advanced structural and/or molecular neuroimaging techniques. Yet, despite remarkable recent interest, CAA remains under-recognised by neurologists and stroke physicians. In this review, a fresh look at key developments in understanding the complex pathophysiology, important clinical and radiological features, diagnostic approaches and prospects for rational therapies for this enigmatic small vessel disorder is provided.

Neurobiology of Aging, 2015

Sporadic inclusion body myositis sIBM APOE TOMM40 Age of onset a b s t r a c t A previous study s... more Sporadic inclusion body myositis sIBM APOE TOMM40 Age of onset a b s t r a c t A previous study showed that, in carriers of the apolipoprotein E (APOE) genotype ε3/ε3 or ε3/ε4, the presence of a very long (VL) polyT repeat allele in "translocase of outer mitochondrial membrane 40" (TOMM40) was less frequent in patients with sporadic inclusion body myositis (sIBM) compared with controls and associated with a later age of sIBM symptom onset, suggesting a protective effect of this haplotype. To further investigate the influence of these genetic factors in sIBM, we analyzed a large sIBM cohort of 158 cases as part of an International sIBM Genetics Study. No significant association was found between APOE or TOMM40 genotypes and the risk of developing sIBM. We found that the presence of at least 1 VL polyT repeat allele in TOMM40 was significantly associated with about 4 years later onset of sIBM symptoms. The age of onset was delayed by 5 years when the patients were also carriers of the APOE genotype ε3/ε3. In addition, males were likely to have a later age of onset than females. Therefore, the TOMM40 VL polyT repeat, although not influencing disease susceptibility, has a disease-modifying effect on sIBM, which can be enhanced by the APOE genotype ε3/ε3.