(Press-News.org) HOUSTON, June 29 -- Many parents have heard the night-time cry of "my ear hurts." For some children, this might happen frequently beginning in infancy and even persist into adulthood. An international consortium led by those at Baylor College of Medicine may have taken the first step on the road to understanding why only some people get frequent painful or chronic middle ear infections. The culprit may be rare genetic variants in a gene called A2ML1.
A report on their work appears online in the journal Nature Genetics.
In studies led by Dr. Regie Lyn P. Santos-Cortez, assistant professor of molecular and human genetics at Baylor, researchers looked for a genetic component to the disorder. Santos-Cortez is not only a genetics researcher, she was also trained as an otolaryngologist in her native Philippines, and she knows the toll such infections take. After graduation, she went on a medical missionary trip to an indigenous Filipino population in one area of the country where most of the people were related.
There she created a family tree or pedigree that identified, among other things, who within the same community suffered from recurrent ear infections and who did not.
"The pedigree was huge," she said. "It was several pages long and wide."
Everyone had similar socioeconomic status, swam in the same sea water, were or had been mostly breastfed, ate the same food, and had the same exposure to cigarette smoke, which made an environmental factor an unlikely cause.
Luckily, next-generation sequencing that allowed her to determine the genetic sequence of several people in the population was available. Without that technological advance, she said, she did not think they could have identified the gene.
Within the indigenous community, she found that 80 percent of those who carry the variant in the A2ML1 gene developed otitis media. They also found the same gene variant in three otitis-prone children in a group in Galveston, Texas.
So far, they have identified this rare genetic cause for susceptibility to middle ear infections in 37 Filipinos, one Hispanic-American and two European-Americans. It is likely that the variant has been present in the population in the Philippines and in Galveston at least 150 years and may even be the result of a "founder" effect, which suggests one person from outside the population, more likely from Spain, brought the gene variant into the two populations.
Additionally, rare A2ML1 variants were identified in six otitis-prone children who were Hispanic- or European-American, and none of these variants occurred in thousands of individuals without otitis media.
She does not think this is the only gene involved in predisposing children to middle ear infections, but it could be an important one. The protein involved may play a role in the immune system that protects the ear. Perhaps the variant somehow derails the protection the protein should provide.
Another gene called alpha 2-macroglobulin or A2M, which encodes a protein that is found at high levels in very infected ears, is formed in such a way that it can trap proteases, enzymes that can kill infectious microbes but can also damage the mucosa of the middle ear if left unchecked.
Because the protein sequences of A2M and A2ML1 are highly identical, they may have similar or overlapping functions and one might compensate for the other when it is non-functional. An antibiotic drug called bacitracin is used in drop form to treat the problem in Europe.
However, because bacitracin dampens the effect of A2M it may not be the best treatment for people who have genetic variants in A2ML1, she said.
"There are many other antibiotic drops on the market," said Santos-Cortez.
The finding of the variant is a start, she said. She and her colleagues hope to look further into the mechanism by which A2ML1 defects cause otitis media susceptibility.
Others who took part in this work include Xin Wang, Anushree Acharya, Izoduwa Abbe, Biao Li, Gao T. Wang and Suzanne M. Leal, all of Baylor; Charlotte M. Chiong, Ma Rina T Reyes-Quintos, Ma Leah C. Tantoco, Marieflor Cristy Garcia, Erasmo Gonzalo D V Llanes, Patrick John Labra, Teresa Luisa I. Gloria-Cruz, Abner L. Chan, Eva Maria Cutiongco-de la Paz and Generoso T. Abes, all of the University of the Philippines Manila-National Institutes of Health; Arnaud P. Giese, Saima Riazuddin and Zubair M. Ahmed, University of Maryland at Baltimore; Joshua D Smith, Jay Shendure, Michael J. Bamshad and Deborah A. Nickerson, all of the University of Washington at Seattle; E. Kaitlynn Allen and Michele M. Sale of the University of Virginia in Charlottesville; Kathleen A. Daly of the University of Minnesota in Minneapolis; Janak A. Patel and Tasnee Chonmaitree of the University of Texas Medical Branch at Galveston.
INFORMATION:
Funding for this work came from the Hearing Health Foundation; Action On Hearing Loss and the National Organization for Hearing Research Foundation (to R.L.P.S.-C.); the University of the Philippines Manila-National Institutes of Health (to G.T.A. and R.L.P.S.-C.); and U.S. National Institutes of Health (Grants U54 HG006493 (to D.A.N.), R01 DK084350 (to M.M.S.), R01 DC003166 (to K.A.D.), R01 DC005841 (to T.C.), R01 DC011803 and R01 DC012564 (to S.R. and Z.M.A.), and R01 DC011651 and R01 DC003594 (to S.M.L.).
Contact:
Glenna Vickers
picton@bcm.edu
713-798-4710
http://www.bcm.edu/news
New research released today in Nature Neuroscience reveals for the first time that pain is processed in male and female mice using different cells. These findings have far-reaching implications for our basic understanding of pain, how we develop the next generation of medications for chronic pain--which is by far the most prevalent human health condition--and the way we execute basic biomedical research using mice.
"Research has demonstrated that men and women have different sensitivity to pain and that more women suffer from chronic pain than men, but the assumption ...
Neighborhood resources to support greater physical activity and, to a lesser extent, healthy diets appear to be associated with a lower incidence of type 2 diabetes, although the results vary by the method of measurement used, according to an article published online by JAMA Internal Medicine.
Type 2 diabetes mellitus (T2DM) is an important cause of death and disability worldwide. Prevention of T2DM has focused largely on behavioral modification. However, the extent to which behavioral modifications will succeed in unsupportive environments remains unknown.
Researcher ...
More than a third of children and teens 17 and younger experienced a physical assault in the last year, primarily at the hands of siblings and peers, according to an article published online by JAMA Pediatrics.
Violence against children is a national and international public health and public policy issue. The U.S. Department of Justice and Centers for Disease Control and Prevention initiated in 2008 the National Survey of Children's Exposure to Violence (NatSCEV) to provide ongoing estimates of a wide range of violence against youth. Assessments have occurred in three-year ...
An 'exhausted' army of immune cells may not be able to fight off infection, but if its soldiers fight too hard they risk damaging the very body they are meant to be protecting, suggests new research from the University of Cambridge.
Inside our bodies are billions of immune cells known as T cells that protect us from infection, fighting off attacks from invading bacteria and viruses, and also from cancer. One teaspoon full of blood alone is believed to have around 5 million T cells. But these cells can also do harm, mistaking our own cells for invaders and attacking them, ...
Pink salmon that begin life in freshwater with high concentrations of carbon dioxide, which causes acidification, are smaller and may be less likely to survive, according to a new study from UBC.
The risks of ocean acidification on marine species have been studied extensively but the impact of freshwater acidification is not well understood. The study is one of the first to examine how rising carbon dioxide levels caused by climate change can impact freshwater fish.
"Most of the work on acidification has been in the ocean, yet 40 per cent of all fish are freshwater. ...
June 29, 2015 - For hikers, football players, endurance athletes, and a growing range of elite and recreational exercisers, the best approach to preventing potentially serious reductions in blood sodium level is to drink when thirsty, according to an updated consensus statement on exercise-associated hyponatremia (EAH). The recommendations appear in the June issue of the Clinical Journal of Sport Medicine, published by Wolters Kluwer.
"Using the innate thirst mechanism to guide fluid consumption is a strategy that should limit drinking in excess and developing hyponatremia ...
ANN ARBOR--Employees seeking to boost their productivity at work should take a nap--yes, sleeping on the job can be a good thing.
A new University of Michigan study finds that taking a nap may be an effective strategy to counteract impulsive behavior and to boost tolerance for frustration.
Napping, the researchers say, can be a cost-efficient and easy strategy to increase workplace safety. In other words, employers may find their employees more productive when the workplace has nap pods in the workplace or extended break times are offered.
It's becoming increasingly ...
Maybe it sounds like a cow and bull story, but researchers in Egypt are developing a biometric identification system for cattle that could reduce food fraud and allow ranchers to control their stock more efficiently. The system described in the International Journal of Image Mining uses the unique features of a prominent part of the animal to identify the beasts. No, it's not hoof prints or an udder body part - it's the bovine muzzle, no pair of which are exactly alike, according to computer scientist Hamdi Mahmoud of BeniSuef University, in Cairo.
Meat products are currently ...
June 29, 2015 - In recent years, a large majority of US plastic surgeons have adopted fat grafting techniques as part of their approach to facelift surgery, reports a study in the July issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS).
Fat grafting--transferring small amounts of the patient's own fat in strategic areas--"has become a common technique utilized by most surgeons today performing facial rejuvenation," according to the new research by Dr. Sammy Sinno, a plastic surgeon at New York ...
As yet another music streaming service comes online to rival the countless available outlets for so many different genres, a new approach to classifying music to make archiving, sorting and music discovery easier is published in the International Journal of Computational Intelligence Studies.
Rare is the musical artist described as genre-defying. Most singers and musicians tend to stick to a particular genre, whether electronic dance music, reggae, classical, folk, jazz, rock or Indian genres such as Bhangra and Ghazal, or any of hundreds of other categories. Listeners ...
