Breaking News
February 16, 2019 - Collaborative material research could advance self-assembling nanomaterials
February 16, 2019 - Researchers take major step in creating technology that mimics the human brain
February 16, 2019 - Erasing memories associated with cocaine use reduces drug seeking behavior
February 16, 2019 - Artificial intelligence can accurately predict prognosis of ovarian cancer patients
February 16, 2019 - Racial disparities in cancer deaths on the decline for America
February 16, 2019 - FDA authorizes new interoperable insulin pump for children, adults with diabetes
February 16, 2019 - Coexisting Medical Conditions, Smoking Explain PTSD-CVD Link
February 16, 2019 - Skin Cancer Screening: MedlinePlus Lab Test Information
February 16, 2019 - ‘Happiness’ exercises can boost mood in those recovering from substance use disorder
February 16, 2019 - Cell manipulation could soon halt or reverse aging
February 16, 2019 - Pumped Breast Milk Falls Short of Breastfed Version
February 16, 2019 - Men’s porn habits could fuel partners’ eating disorders, study suggests
February 16, 2019 - Rapid progression of age-related diseases may result from formation of vicious cycles
February 16, 2019 - Immune checkpoint molecule protects against future development of cancer
February 16, 2019 - New method produces hydrogels that have properties similar to cells’ environment
February 16, 2019 - $4.1 million funding for heart research on Valentine’s Day
February 16, 2019 - General anesthesia in early infancy unlikely to have lasting effects on developing brains
February 16, 2019 - New breakthroughs for muscular dystrophy research
February 16, 2019 - First Opinion: Embryo editing for higher IQ is a fantasy. Embryo profiling for it is almost here
February 16, 2019 - Vapers develop cancer-related gene deregulation as cigarette smokers
February 16, 2019 - Bringing Antimicrobial Susceptibility Testing (AST) to the Community
February 16, 2019 - Decolonization protocol after hospital discharge can prevent dangerous infections
February 16, 2019 - New technique using patients’ own modified cells could help treat Crohn’s disease
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Blood clot discovery could lead to development of better treatments for blood diseases
February 16, 2019 - Intervention can increase exclusive breastfeeding rates
February 16, 2019 - New project explores how gaming technologies can help cancer patients communicate better
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
February 15, 2019 - Beta wave control in Parkinson’s diseased brain could be a potential therapy
February 15, 2019 - Media representations of love may justify gender-based violence in young people
February 15, 2019 - Yoga May Help With Rheumatoid Arthritis Symptoms, Severity
February 15, 2019 - Obstructive sleep apnea linked to inflammation, organ dysfunction
February 15, 2019 - Master your mind: A challenge from WELL for Life
February 15, 2019 - Why Some Brain Tumors Respond to Immunotherapy
February 15, 2019 - Must-Reads Of The Week From Brianna Labuskes
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Excessive daytime sleepiness in OSA patients linked to greater risk for cardiovascular diseases
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - Celiac disease may be caused by stomach bug in childhood
February 15, 2019 - NHS performance figures highlight the true scale of Emergency Department crisis
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
New genetic insight could help treat rare debilitating heart and lung condition

New genetic insight could help treat rare debilitating heart and lung condition

image_pdfDownload PDFimage_print
Credit: CC0 Public Domain

The largest study of genetic variation in patients with pulmonary arterial hypertension has associated two important genes with the disease.

In collaboration with institutes from Europe and Northern America, researchers from Imperial College London have conducted the largest genetic analysis to date of 2,000 patients with pulmonary arterial hypertension (PAH) and identified associations with two genes.

PAH is a rare form of pulmonary hypertension that affects the blood vessels in the lungs, causing high blood pressure that can lead to heart failure. The disease is often fatal and, on average, patients survive 5-6 years after diagnosis. Sufferers feel breathless and tired, with symptoms worsening during exercise.

The research is the first to demonstrate that variations in the SOX17 gene and the HLA-DPB1 gene were associated with PAH. Insight into the genetic mechanisms behind this life-threatening disease could help inform treatments and identify new therapeutic targets.

Common genetic variation

PAH can be related to other conditions such as congenital heart problems, connective tissue disease, and HIV but for many sufferers, PAH is either inherited (HPAH) or arises for no known reason, which is known as idiopathic PAH (IPAH). Around 1,500 people in the UK have either HPAH or IPAH and 10 per cent of sufferers die each year. PAH affects more women than men, typically in their 30s and 40s.

Previous research has identified some of the rare genetic mutations behind inherited PAH, but little is known about the common genetic variation responsible for smaller differences between patients and the variation in their response to treatments. Current treatments include medicines to help prevent blood clots, diuretics and specialist treatments to relax the arteries in the lungs.

Published in The Lancet Respiratory Medicine, the study aggregated data from four international cohorts from Europe and North America on patients with heritable or idiopathic PAH. UK data was from the National Institute for Health Research BioResource (NIHR BioResource) – Rare Diseases and the British Heart Foundation Pulmonary Arterial Hypertension (BHFPAH) study.

The analysis took a genome-wide association (GWAS) approach, which examined millions of common variants covering the genome. The research identified three genetic signals associated with PAH: two of these were next to the SOX17 gene in the region that ‘loops back’ to regulate the levels of SOX17 and the third signal was within the HLA-DPB1 gene.

Lead author and British Heart Foundation Intermediate Basic Science Fellow Dr. Christopher Rhodes from Imperial’s Department of Medicine, said: “This is the first study at the scale required to look at how common genetic variations influence PAH, which could help us understand variations in how the disease presents itself and how patients respond to treatments.

“We were very lucky to pool data with our collaborators as this has provided us with a large enough sample to study these more subtle genetic variations in a statistically meaningful way. Out of the 23,000 genes in the whole genome we have found that PAH has significant associations with two genes, SOX17 and HLA-DPB1, providing strong evidence that these genes play an important role in PAH. This opens up exciting possibilities for future research into new therapies.”

Susceptibility and disease progression

SOX17 is instrumental in the development of the endothelial cells that line the arteries in the lung, indicating it could be associated with the structural changes that make patients susceptible to PAH. Previous research has shown that rare genetic variation in SOX17 can cause heritable PAH.

The other gene identified by the study, HLA-DPB1, is involved in controlling the immune response and plays a role in disease progression. The analysis identified different variations or alleles of HLA-DPB1 within PAH patients and found that the number of years that patients survived after diagnosis depended on which versions were active. About 5 per cent of patients have two copies of the C allele of HLA-DPB1 and on average they survived 13.5 years, whereas the majority of patients (69 per cent) have two copies of the T allele and survived on average 7 years.

One of the variations of HLA-DPB1 identified in the study has also been linked with susceptibility to lung diseases caused by exposure to hard metals such as berylliosis.

Professor Martin Wilkins, a senior author and Head of the Department of Medicine at Imperial College London, said:

“This study represents the enormous efforts of an international collaboration and the generous participation of many patients, making it the largest genetic study of PAH to date. The findings raise the importance of including the genotype as a factor when interpreting the results of clinical studies, as it may be that some patients deteriorate at a rate determined by their genotype, rather than at a rate determined by a new treatment.

“The discovery of a common variant that operates through a gene, SOX17, that is mutated in a few patients with the disease suggests that SOX17 may be more commonly involved in pulmonary hypertension than previously thought. This has implications for the development of new treatments that might come from further work on SOX17.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation said:

“PAH is a rare but devastating condition which usually strikes people in the prime of their life.

“This is scientific collaboration at its best. This international team has made real gains in our understanding of PAH by identifying two important genes which contribute to its development, laying the essential groundwork we need to develop new treatments in future.”


Explore further:
Genetic study could lead to new treatments for sufferers of pulmonary arterial hypertension

More information:
Christopher J Rhodes et al. Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis, The Lancet Respiratory Medicine (2018). DOI: 10.1016/S2213-2600(18)30409-0

Journal reference:
Lancet Respiratory Medicine

Provided by:
Imperial College London

Tagged with:

About author

Related Articles