Breaking News
January 23, 2019 - Medical expert advises people with epilepsy not to stockpile medicines
January 23, 2019 - Bedfont to exhibit NObreath FeNO monitor at Arab Health 2019
January 23, 2019 - Nicotinamide riboside supplementation confers significant physiological benefits to mothers and offspring
January 23, 2019 - Increasing temperatures may help preserve crop nutrition
January 23, 2019 - Many Oncologists in the Dark About LGBTQ Health Needs
January 23, 2019 - Epigenetic change causes fruit fly babies to inherit diet-induced heart disease
January 23, 2019 - Erasing memories could reduce relapse rates among drug addicts
January 23, 2019 - African Americans who smoke cigarettes are more likely to develop peripheral artery disease
January 23, 2019 - Unique data combination helps FinnGen researchers to fund links between genetic factors and health
January 23, 2019 - Parents’ mental health problems associated with reactive attachment disorder in children
January 23, 2019 - Graphene Flagship project studies impact of graphene and related materials on our health
January 23, 2019 - The connection between the Pope and contraceptive pills
January 23, 2019 - Prior dengue infection could protect children from symptomatic Zika
January 23, 2019 - VISTA checkpoint implicated in pancreatic cancer immunotherapy resistance
January 23, 2019 - The Tiny Camera That Could Revolutionize Cardiovascular Surgery
January 23, 2019 - Peptide isolated from soil fungi has antitumor and antibacterial properties
January 23, 2019 - TGen identifies polio-like virus as potential cause of Acute Flaccid Myelitis outbreak
January 23, 2019 - Migrants and refugees do not bring disease and are at greater health risk themselves says WHO
January 23, 2019 - Examing the effects of menopause in workplace
January 23, 2019 - Enemy number 1 – Air pollution and climate change top of WHO agenda
January 23, 2019 - Two Positive Phase III studies of Tafenoquine for the Radical Cure of Plasmodium vivax Malaria Published in The New England Journal of Medicine
January 23, 2019 - World Trade Center responders at increased risk for head and neck cancers
January 23, 2019 - Low-sugar diet leads to significant improvement in nonalcoholic fatty liver disease in boys
January 23, 2019 - Chaos in bodily regulation can optimize our immune system, finds study
January 23, 2019 - Short, text-based exercises can increase happiness for adults recovering from substance use disorders
January 23, 2019 - Body size may have greater influence on women’s lifespan than men
January 23, 2019 - Groundbreaking tool helps visualize neuronal activity with near-infrared light
January 23, 2019 - Prior dengue immunity in children may be protective against symptomatic Zika
January 23, 2019 - Holocaust survivors with PTSD and their offspring exhibit more unhealthy behavior patterns
January 23, 2019 - Scientists discover new genetic mutations causing inherited deaf-blindness
January 23, 2019 - UC team designs new naloxone-dispensing smart device
January 23, 2019 - Torrent Pharmaceuticals Limited Issues Voluntary Nationwide Recall of Losartan Potassium Tablets, USP and Losartan Potassium and Hydrochlorothiazide Tablets, USP
January 23, 2019 - Brain activity shows development of visual sensitivity in autism
January 23, 2019 - Two hour gap between dinner and sleep is overrated says Japanese research
January 23, 2019 - Fear and embarrassment are causing smear test numbers to plummet
January 23, 2019 - Protein-secreting device implanted in epileptic rats reduces seizures, improves cognition
January 23, 2019 - Reintroduction project recovers current wild population of green turtle in Cayman Islands
January 23, 2019 - Cancer survivors face greater financial burden related to medical bills
January 23, 2019 - PSA screening reduces prostate cancer deaths by 30%
January 23, 2019 - LSTM receives grant to help improve health of people living in informal settlements
January 23, 2019 - Hemochromatosis Mutation Linked to Other Morbidity
January 23, 2019 - Why early diagnosis of autism should lead to early intervention
January 23, 2019 - Aspirin May Lower Stroke Risk in Women with History of Preeclampsia
January 23, 2019 - Exposure to certain chemicals may be linked to decrease in blood pressure during pregnancy
January 23, 2019 - Bowel cancer on the rise among younger Australians
January 23, 2019 - Scientists have reversed memory loss in a mouse model of Alzheimer’s
January 23, 2019 - Defective molecular master switch could lead to age-related macular degeneration
January 23, 2019 - Researchers identify how concussions may contribute to seizures
January 23, 2019 - Short interval between last meal of the day and bedtime may not affect blood glucose levels
January 23, 2019 - Still Too Many Highway Deaths Tied to Speeding
January 23, 2019 - Prenatal valproate exposure linked to increased ADHD risk
January 23, 2019 - Compound identified that may help treat heart failure
January 23, 2019 - Undiagnosed Asthma in Urban Adolescents May Be Common
January 23, 2019 - Study describes metabolism of intestinal microbiota in babies for the first time
January 22, 2019 - Study links concussions to development of epilepsy
January 22, 2019 - Specialist-led hospital bereavement service may help restrain legal action after difficult deaths
January 22, 2019 - Genetic study reveals possible new routes to treating osteoarthritis
January 22, 2019 - Blood test may detect early signs of lung-transplant rejection
January 22, 2019 - Blood marker could aid in early prediction of Alzheimer’s progression
January 22, 2019 - Orthodontic treatment does not guarantee future dental health
January 22, 2019 - Rutgers researchers discover cause of bone loss in people with joint replacements
January 22, 2019 - Diversity among rural Africans extends to their gut microbiomes
January 22, 2019 - Newly developed biological system lets cells to create self-curving cornea
January 22, 2019 - VTv Therapeutics Announces Publication of Comprehensive Data in Science Translational Medicine Detailing the Discovery and Clinical Development of TTP399, including Results of Phase 2 AGATA Study
January 22, 2019 - about one in three adults with prediabetes has arthritis
January 22, 2019 - A look at how data is democratizing health care
January 22, 2019 - Alcohol-Linked Disease Overtakes Hep C As Top Reason For Liver Transplant
January 22, 2019 - Researchers identify new genes linked with age-related macular degeneration
January 22, 2019 - MPFI researchers identify synaptic logic for connections between two brain hemispheres
January 22, 2019 - New approach to reduce toxic protein production in ALS
January 22, 2019 - New study extends our knowledge of the link between miRNAs and cancer
January 22, 2019 - Asthma, eczema are not barriers to active lifestyle in teenagers
January 22, 2019 - Genetic changes may predict likelihood of relapse in breast cancer patients
January 22, 2019 - Antiepileptic drug use by people with Alzheimer’s disease linked to accumulation of hospital days
January 22, 2019 - IUPUI researcher receives $2.85 million grant to find ways to improve bone strength
January 22, 2019 - Precision medicine can help keep astronauts healthy during deep space missions
January 22, 2019 - Detecting signs of neurodegeneration earlier and more accurately
January 22, 2019 - Mouse studies challenge ‘inhibition’ theory of autism
January 22, 2019 - SSB launches BIOSTAT RM TX single-use bioreactor for producing consistent quality cellular products
January 22, 2019 - Experimental drug can positively modify key characteristic behavior in FXS patients
Scientists identify six new gene regions that may help treat type 1 diabetes

Scientists identify six new gene regions that may help treat type 1 diabetes

image_pdfDownload PDFimage_print

Six novel chromosomal regions identified by scientists leading a large, prospective study of children at risk for type 1 diabetes will enable the discovery of more genes that cause the disease and more targets for treating or even preventing it.

The TEDDY study’s international research team has identified the new gene regions in young people who have already developed type 1 diabetes or who have started making antibodies against their insulin-producing cells, often a precursor state to the full-blown disease that leads to a lifetime of insulin therapy.

Their analysis of 5,806 individuals published in the Journal of Autoimmunity also confirmed three regions already associated with one of those related conditions.

“We want to build a more precise profile of who will get this disease and when,” says Dr. Jin-Xiong She, director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia at Augusta University, principal investigator of TEDDY’s Georgia/Florida site and the study’s corresponding author.

In keeping with their theory that two subtypes of type 1 diabetes will become clear from longitudinal studies of those at risk, the international TEDDY team also found different chromosomal regions were associated with which autoantibody shows up first in a patient, a sign his immune system is turning on his pancreas.

They looked at two top autoantibodies: one directly against insulin, called IAA, and one called GADA, against the enzyme glutamate decarboxylase, which regulates the insulin-producing beta cells in the pancreas. About 90 percent of patients with type 1 diabetes have one or the other autoantibody first and many eventually end up with both, She says. The second autoantibody may surface in a few days or even years later.

“There is mounting evidence that we have at least two major subtypes of type 1 diabetes, based on the autoantibodies children have. Now we have found a genetic basis that supports that,” says She, Georgia Research Alliance Eminent Scholar in Genomic Medicine.

TEDDY – The Environmental Determinants of Diabetes in the Young – is an international initiative following almost 9,000 children for 15 years in a strategic and rare opportunity to watch how genetics and environmental factors collide to cause disease, She says. An original goal of TEDDY was to better determine which genetic variations correlate with progression or lack of progression to type 1 diabetes.

For this particular pursuit, they focused on the 5,806 Caucasian TEDDY participants, because of genetic differences in different ethnic groups. They also focused on non-HLA genes, says Dr. Ashok Sharma, MCG bioinformatics expert and the study’s first author.

Most genes known to be associated with type 1 diabetes – including those currently considered the top two high-risk genes, which are the ones TEDDY screens for – are classified as human leukocyte antigen, or HLA genes. It’s a logical association since HLA genes regulate our immune system, says Sharma.

But in their comprehensive effort to better identify children at highest risk of disease – and ideally one day intervene – this particular search focused on non-HLA genes. “By study design we were looking for them,” Sharma says.

“With HLA genes you can achieve a certain level of accuracy in identifying high-risk individuals,” says She. “But if we can add additional genes into the screening, we can refine the prediction of the disease, we can increase the accuracy, we can probably even identify higher percentages of at-risk individuals.”

“It’s not monogenic, there are many genes involved,” Sharma says of type 1 diabetes, a condition that affects 1 in 300 people in the United States by age 18, according to the National Institutes of Health.

Which of those genes are involved also varies by individual. Sharma and She note the reality that not all patients with the high-risk genes even get the disease, although they still don’t know why.

One of the many points they hope TEDDY clarifies is if or how these genetics along with environmental factors – like childhood infections or even what children eat – conspire to cause actual disease. Genetic factors are comparatively easier to identify, and should also help identify environmental factors, they say.

For this study, the scientists also started with 176,586 SNPs, or single nucleotide polymorphisms. A nucleotide is a basic building block of our genetic information. In the case of DNA, those are A, C, T and G, chemical bases that can be arranged in seemingly endless potential orders. SNPs are genetic variations – one letter replaced by another – that scientists are using increasingly to figure out which occur more or less often in people with a certain condition or disease.

The SNPs examined by TEDDY scientists were already associated with other autoimmune diseases like rheumatoid arthritis or celiac disease, but not type 1 diabetes, Sharma says. They determined which of these SNPs are different in TEDDY participants who had developed type 1 diabetes versus those who had Islet cell autoantibodies versus those who still had neither.

Previous research has shown that the same genes are not always associated with IA and actual type 1 diabetes.

In fact, while Islet cell autoantibodies, or IA, are considered a red flag for type 1 diabetes, not every child with IA will progress to full-blown disease, She says, although multiple autoantibodies definitely increase that risk. In fact, different genes may play a role in IA development while others play a role in disease progression, the TEDDY scientists write.

While the SNPs themselves may or may not have a direct functional consequence, they are in close proximity to a gene that does, says She. “It’s a marker,” he says, that will enable the scientists to more efficiently and effectively identify causative genes.

“We are using SNPs but not as an endpoint,” Sharma notes. “We want to find out the genes which are there,” a focal point for the work now underway.

Key to the work already complete, is how closely and long TEDDY participants are followed. Normally gene identification starts with what is called a case-control design, in which genetic variations are compared between patients with a condition and healthy individuals, to look for differences that may contribute to the disease.

While standard cross-sectional, or case-control studies haven’t shown a huge impact from non-HLA genes, they only provide a “snapshot’ of what is happening with both patients and controls alike, the scientists say. With the prospective and longitudinal TEDDY, the scientists are literally watching the disease occur – or not – in high-risk young people.

In fact, this is the first major study regarding gene identification for any disease that uses this sort of longitudinal information, She says.

As with many things, timing is everything, and the TEDDY perspective sharpens the search, particularly for important non-HLA genes by adding the “time to disease” perspective, She says.

Source:

Medical College of Georgia at Augusta University

Tagged with:

About author

Related Articles