Gene behind freckles, brown hair and blue eyes found

November 23, 2013

boards.weddingbee.comWashington, Nov 23: In the study of Icelanders, researchers uncovered an intricate pathway involving the interspersed DNA sequence, or non-coding region, of a gene that is among a few dozen associated with human pigmentation traits.

It is more common to find people with ancestors from geographic locations farther from the equator, such as Iceland, who have less pigment in their skin, hair and eyes.

The researchers, including scientists from the National Human Genome Research Institute (NHGRI), analysed data from a genome-wide association study (GWAS) of 2,230 Icelanders.

A GWAS compares hundreds of thousands of common differences across individuals' DNA to see if any of those variants are associated with a known trait.

"This study explains a complex molecular pathway that may also contribute insights into skin diseases, such as melanoma, which is caused by the interaction of genetic susceptibility with environmental factors," said NHGRI Scientific Director Dan Kastner.

Researchers focused on the interferon regulatory factor 4 (IRF4) gene, previously associated with immunity. IRF4 makes a protein that spurs production of interferons, proteins that fight off viruses or harmful bacteria.

The researchers noted from genomic databases that the IRF4 gene is expressed at high levels only in lymphocytes, a type of white blood cell important in the immune system, and in melanocytes, specialized skin cells that make the pigment melanin. The new study established an association between the IRF4 gene and the pigmentation trait.

"Genome-wide association studies are uncovering many genomic variants that are associated with human traits and most of them are found in non-protein-coding regions of the genome," said William Pavan, co-author and senior investigator, Genetic Disease Research Branch, NHGRI.

The Icelandic GWAS yielded millions of variants among individuals in the study. The researchers narrowed their study to 16,280 variants located in the region around the IRF4 gene.

They used an automated fine-mapping process to explore the set of variants in IRF4 in 95,085 people from Iceland. The data revealed that a variant in a non-coding, enhancer region that regulates the IRF4 gene is associated with the combined trait of sunlight sensitivity, brown hair, blue eyes and freckles.

The study was reported in the journal Cell.

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January 26,2020

High-protein diets may help people lose weight and build muscle, but there is a downside to it --a greater heart attack risk. Researchers now report that high-protein diets boost artery-clogging plaque.

The research in mice showed that high-protein diets spur unstable plaque -- the kind most prone to rupturing and causing blocked arteries.

More plaque buildup in the arteries, particularly if it's unstable, increases the risk of heart attack.

"There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years," said senior author Babak Razani, associate professor at Washington University School of Medicine in St. Louis, Missouri.

"But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health," Razani added.

The researchers studied mice who were fed a high-fat diet to deliberately induce atherosclerosis, or plaque buildup in the arteries.

Some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.

The mice on the high-fat, high-protein diet developed worse atherosclerosis -- about 30 per cent more plaque in the arteries -- than mice on the high-fat, normal-protein diet, despite the fact that the mice eating more protein did not gain weight, unlike the mice on the high-fat, normal-protein diet.

"A couple of a scoop of protein powder in a milkshake or smoothie adds something like 40 grams of protein -- almost equivalent to the daily recommended intake," Razani said.

"To see if protein has an effect on cardiovascular health, we tripled the amount of protein that the mice receive in the high-fat, high-protein diet -- keeping the fat constant. Protein went from 15 per cent to 46 per cent of calories for these mice".

Plaque contains a mix of fat, cholesterol, calcium deposits and dead cells. Past work by Razani's team and other groups has shown that immune cells called macrophages work to clean up plaque in the arteries.

But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.

"In mice on the high-protein diet, their plaques were a macrophage graveyard," Razani informed.

To understand how high dietary protein might increase plaque complexity, Razani and his colleagues also studied the path protein takes after it has been digested -- broken down into its original building blocks, called amino acids.

"This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques," said Razani.

"This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease," he added.

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Agencies
February 11,2020

Using smartphone for long hours every day may do you more harm than you can probably think of. Researchers have found that spending a lot of time with the device and on social media may lead to mental distress and suicidality among adolescents.

The findings, published in the journal CMAJ (Canadian Medical Association Journal) contains guidance for physicians, parents and teachers on how to help teenagers manage smartphone and social media use for a healthy balance between sleep, academic work, social activity, interpersonal relationships and online activity.

"Physicians, teachers and families need to work together with youth to decrease possible harmful effects of smartphones and social media on their relationships, sense of self, sleep, academic performance, and emotional well-being," said lead author of the study Elia Abi-Jaoude from Toronto Western Hospital in Canada.

This review of evidence, led by the Hospital for Sick Children (SickKids), focuses on smartphone use and does not consider online gaming.

"For adolescents today, who have not known a world without social media, digital interactions are the norm, and the potential benefits of online access to productive mental health information -- including media literacy, creativity, self-expression, sense of belonging and civic engagement -- as well as low barriers to resources such as crisis lines and Internet-based talking therapies cannot be discounted," the authors wrote.

The researchers recommend that doctors should ask teenagers to reduce social media use rather than eradicate it completely and encourage parents to be part of the conversations.

Parents should discuss appropriate smartphone use with teenagers to determine together how to reduce risks and set boundaries.

A recent poll from the US indicates that 54 per cent of teenagers think they spend too much time on their smartphones and about half said they were cutting back on usage.

"Encouragingly, youth are increasingly recognising the negative impact of social media on their lives and starting to take steps to mitigate it," the authors wrote.

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Agencies
May 19,2020

Researchers have found that patients with peripheral artery disease or stroke were less likely to receive recommended treatments to prevent heart attack than those with coronary artery disease. All three are types of atherosclerotic cardiovascular disease.

Depending on the location of the blockage, atherosclerosis increases the risk for three serious conditions: coronary artery disease, stroke and peripheral artery disease.

"Our study highlights the need for public health campaigns to direct equal attention to all three major forms of atherosclerotic cardiovascular disease," said senior study author Erin Michos from the Johns Hopkins University in the US.

"We need to generate awareness among both clinicians and patients that all of these diseases should be treated with aggressive secondary preventive medications, including aspirin and statins, regardless of whether people have heart disease or not," Michos added.

Since atherosclerosis can affect arteries in more than one part of the body, medical guidelines are to treat coronary artery disease, stroke and peripheral artery disease similarly with lifestyle changes and medication, including statins to lower cholesterol levels and aspirin to prevent blood clots.

Lifestyle changes include eating a healthy diet, being physically active, quitting smoking, controlling high cholesterol, controlling high blood pressure, treating high blood sugar and losing weight.

What was unclear was if people with stroke and peripheral artery disease received the same treatments prescribed for those with coronary artery disease.

This study compared more than 14,000 US adults enrolled in the 2006-2015 Medical Expenditure Panel Survey, a national survey of patient-reported health outcomes and conditions, and health care use and expenses.

Slightly more than half of the patients were men, the average age was 65, and all had either coronary artery disease, stroke or peripheral artery disease.

These individuals were the representative of nearly 16 million US adults living with one of the three forms of atherosclerotic cardiovascular disease.

Compared to participants with coronary artery disease, participants with peripheral artery disease were twice more likely to report no statin use and three times more likely to report no aspirin use.

Additionally, people with peripheral artery disease had the highest, annual, total out-of-pocket expenditures among the three atherosclerotic conditions.

The findings showed that participants with stroke were more than twice as likely to report no statin or aspirin use.

Moreover, those with stroke were more likely to report poor patient-provider communication, poor health care satisfaction and more emergency room visits.

"Our study highlights a missed opportunity for implementing life-saving preventive medications among these high-risk individuals," Michos said.

The study was presented in the virtual conference at the American Heart Association's Quality of Care & Outcomes Research Scientific Sessions 2020.

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