Genetic variation and exposure to pesticides both appear to affect risk for Parkinson's disease. A new study has found a connection between these two risk factors, in a way that highlights a role for immune responses in progression of the disease.
The results are published in the inaugural issue of NPJ Parkinson's Disease.
The findings implicate a type of pesticide called pyrethroids, which are found in the majority of commercial household insecticides, and are being used more in agriculture as other insecticides are being phased out. Although pyrethroids are neurotoxic for insects, exposure to them is generally considered safe for humans by federal authorities.
The study is the first making the connection between pyrethroid exposure and genetic risk for Parkinson's, and thus needs follow-up investigation, says co-senior author Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine.
The genetic variation the team probed, which has been previously tied to Parkinson's in larger genome-wide association studies, was in a non-coding region of a MHC II (major histocompatibility complex class II) gene, part of a group of genes that regulate the immune system.
"We did not expect to find a specific association with pyrethroids," Tansey says. "It was known that acute exposure to pyrethroids could lead to immune dysfunction, and that the molecules they act on can be found in immune cells; now we need to know more about how longer-term exposure affects the immune system in a way that increases risk for Parkinson's."
"There is already ample evidence that brain inflammation or an overactive immune system can drive the progression of Parkinson's. What we think may be happening here is that environmental exposures may be altering some people's immune responses, in a way that promotes chronic inflammation in the brain."
For this study, Emory investigators led by Tansey and Jeremy Boss, PhD, chair of microbiology and immunology, teamed up with Stewart Factor, DO, head of Emory's Comprehensive Parkinson's Disease Center, and public health researchers from UCLA led by Beate Ritz, MD, PhD. The first author of the paper is MD/PhD student George T. Kannarkat.
The UCLA researchers used a California state geographical database covering 30 years of pesticide use in agriculture. They defined exposure based on proximity (someone's work and home addresses), but did not measure levels of pesticides in the body. Pyrethroids are thought to decay relatively quickly, especially in sunlight, with half-lives in soil of days to weeks.
In a group of 962 people from California's Central Valley, a common MHC II variant combined with above-average exposure to pyrethroid pesticides to increase the risk of Parkinson's disease. The riskiest form of the gene (where an individual is carrying two risk alleles) was found in 21 percent of Parkinson's patients and 16 percent of controls.
In this group, genes or pyrethroid exposure by themselves did not significantly increase Parkinson's risk, but together, they did. People with more-than-average exposure to pyrethroids and carrying the riskiest form of the MHC II gene had 2.48 times more risk for Parkinson's than less-exposed people with the least risky gene form. Exposure to other types of pesticides such as organophosphates or paraquat did not heighten risk in the same way.
Larger genetic studies (some including Factor and his patients) have previously identified variations in MHC II genes as having connections to Parkinson's. Puzzlingly, the same genetic variants affect Parkinson's risk differently in Caucasian/European and Chinese populations. MHC II genes are highly variable between individual humans; that's why they play a big role in organ transplant matching.
Other experiments showed that the genetic variant connected to Parkinson's is connected with immune cell function. In a group of 81 Parkinson's patients and control participants from Emory of European ancestry the immune cells from people who had the higher-risk MHC II gene variant studied in California displayed more MHC molecules on their surfaces, the researchers found.
MHC molecules are central to the process of "antigen presentation," a driver for T cells to become activated and have the rest of the immune system get involved. Heightened expression of MHC II was present in resting cells from both Parkinson's patients and healthy controls; but greater responsiveness to immune challenges were observed in Parkinson's patients with the higher risk genotype.
The authors conclude: "Our data suggest that cellular biomarkers (like MHC II activation) may prove more useful than soluble molecules in plasma and cerebrospinal fluid to identify individuals at risk for disease or for patient recruitment into neuroprotective trials testing immunomodulatory drugs."
Our recent news item on Emory pathologist Keqiang Ye’s obesity-related research (Molecule from trees helps female mice only resist weight gain) understates how many disease models the proto-drug he and his colleagues have discovered, 7,8-dihydroxyflavone, can be beneficial in. We do mention that Ye’s partners in Australia and Shanghai are applying to begin phase I clinical trials with a close relative of 7,8-dihydroxyflavone in neurodegenerative diseases.
The idea that particular lipid components, such as omega-3 fatty acids, promote health is quite familiar, so the finding that the lipid oleoylethanolamide or OEA extends longevity in the worm C. elegans is perhaps not so surprising. However, a recent paper in Science is remarkable for what it reveals about how OEA exerts its effects.
Scientists at Baylor College of Medicine led by Meng Wang, with some help from biochemists Eric Ortlund and Eric Armstrong at Emory, discovered that OEA is a way one part of the cell, the lysosome, talks to another part, the nucleus. Lysosomes are sort of recycling centers/trash digesters (important for autophagy) and the nucleus is the control tower for the cell. The authors show that starting in lysosomes, OEA travels to the nucleus and activates nuclear hormone receptors (the Ortlund lab’s specialty). Read more
A team of researchers has discovered a genetic syndrome that causes childhood obesity, intellectual disability and seizures. The syndrome comes from an “unbalanced” chromosomal translocation: affected individuals have additional copies of genes from one chromosome and fewer copies of genes from another.
Katie Rudd, PhD, assistant professor of human genetics at Emory University School of Medicine, is senior author of the paper. Research specialist Ian Goldlust, now a graduate student in the NIH-Oxford-Cambridge Scholars Program, is the first author. Co-authors include investigators from around the USA and Australia.
Rudd’s team was able to connect the contribution of one gene, GNB3, among many involved in the translocation, to the obesity aspect of the syndrome. Her lab created a mouse model with an extra copy of the GNB3 gene and found that the mice are obese. The mice are on average 6 percent (males) or 10 percent (females) heavier.
Rudd says her work was greatly assisted by collaboration with the Unique Rare Chromosome Disorder Support Group, a UK-based charity. Within Unique, a few parents had together found that their children had translocations involving the same chromosomes and similar symptoms. They contacted Rudd and helped her find additional affected families. Her study includes seven unrelated patients.
“It really was a group effort, and Unique was the linchpin,” she says. “Managing to find seven families with exactly the same rare translocation would have been extremely difficult otherwise.”
In America’s battle against obesity, there is some good news. According to a study conducted by Emory researchers, Americans consumed nearly a quarter less added sugars in 2008 than they did 10 years earlier.
The study, published in the American Journal of Clinical Nutrition in July 2011, found that the consumption of added sugars, such as those found in sodas, sports drinks, juices and sweetened dairy products, decreased among all age groups over a decade. The largest decrease came in the consumption of sodas, traditionally the largest contributor to added sugar consumption, according to Jean Welsh, MPH, PhD, RN, study author and post-doctoral fellow in pediatric nutrition at Emory University School of Medicine.
“While we were hopeful this would be the case, we were surprised when our research showed such a substantial reduction in the amount of added sugar Americans are consuming,” said Welsh. “We’re hopeful this trend will continue.”
So, why the change? One of Welsh’s partners in the study, Miriam Vos, MD, MSPH, an assistant professor of pediatrics in the Emory University School of Medicine, and a physician on staff at Children’s Healthcare of Atlanta, attributes much of the shift to public education.
“Over the past decade, there has been a lot of public health awareness about obesity and nutrition, and I think people are starting to get the message about sugar,” says Vos. “We’re not trying to send a message that sugar is inherently bad. It’s more that the large amounts of sugar we consume are having negative effects on our health, including increasing our risk of obesity, diabetes and cardiovascular disease.”
The study interpreted data of 40,000 people’s diets collected by the Centers for Disease Control and Prevention (CDC) over 10 years. From the surveys, researchers were able to calculate how much added sugar – that is sugar that is not originally part of a food – that Americans are consuming. In 1999-2000, the typical person’s daily diet included approximately 100 grams of added sugar, a number that had dropped to 77 grams by 2007 and 2008.
While the study shows that the amount of added sugar Americans are consuming is lower, it doesn’t mean the amount is low enough.
“The American Heart Association recommends that we get about five percent of our calories from added sugars,” says Vos. “In 1999 to 2000, people were consuming about 18 percent of their calories from added sugars. Over 10 years, that amount decreased to 14.5 percent of our daily calories, which is much better. But, clearly, 14.5 percent is still three times more than what is considered a healthy amount. We’re on the right track, but we still have room for improvement.”
The obesity epidemic took center stage at this year’s American Association of Clinical Chemistry (AACC) Annual Meeting. Several Emory experts took the podium to further explore obesity not only as a public health problem, but also as an issue that is changing the way we diagnose diseases and treat health issues in children.
Jeffrey Koplan, MD, MPH
Jeffrey Koplan, MD, MPH, director of the Emory Global Health Institute, led one of the meeting’s plenary sessions, emphasizing that obesity must be fought with changes in both public policy and personal decision-making. Koplan also noted that strategies to address obesity must be localized to fit each community because eating and exercise habits are often culturally specific.
Rising rates of obesity also are changing the way physicians and researchers define and diagnose certain diseases, including metabolic syndrome, a cluster of risk factors including insulin resistance, high blood pressure, cholesterol abnormalities and an increased risk for clotting. The common thread among patients with metabolic syndrome is that they are often overweight or obese.
Ross Molinaro, PhD
Pathologist Ross Molinaro, PhD, medical director of the Core Laboratory at Emory University Hospital Midtown and co-director of the Emory Clinical Translational Research Laboratory, presented insights into the important role of lab testing in the definition and diagnosis of metabolic syndrome. In addition to new markers, Molinaro addressed the global prevalence of metabolic syndrome and the evolving criteria for diagnosis.
Miriam Vos, MD, MSPH
Responding to their members’ demand for more information on how obesity affects children, the AACC hosted a full-day symposium on pediatric obesity and related health complications such as diabetes and high blood pressure. Miriam Vos, MD, MSPH, assistant professor of pediatrics in Emory School of Medicine and a physician at Children’s Healthcare of Atlanta described non-alcoholic fatty liver disease as an increasingly common complication of childhood obesity that can cause inflammation and scarring of the liver.
Stephanie Walsh, MD
Stephanie Walsh, MD, assistant professor of pediatrics in Emory School of Medicine and medical director of child wellness at Children’s Healthcare of Atlanta, leads Children’s efforts in preventing and treating childhood obesity in Georgia, which currently has the second highest rate of childhood obesity in the country. Walsh addressed the effect of Children’s wellness initiative, called Strong4Life, on childhood obesity prevention in Georgia.
“From those in the lab, to those in clinic, to those who strategize and implement public health campaigns, we’re all going to need to work together to protect our children’s future,” says Walsh.
Sperling and his panel colleagues reviewed information about 20 well-known diets, from Atkins to Zone, and rated each one on specific measures such as safety, easiness to follow and nutritional completeness.
Using the experts’ ratings, U.S. News developed five diet categories to address a broad range of consumers’ dieting goals and needs including Best Diabetes Diets, Best Heart Diets, Best Weight Loss Diets and Best Overall. “The goal of the Best Diets rankings is to help consumers find authoritative guidance on healthful diets that will work for them over the long haul,” said Lindsay Lyon, U.S. News‘s Health News Editor.
Weight Watchers ranked first in the Weight Loss category. Tied for number two were Jenny Craig and the Raw Food Diet, an approach that challenges dieters to avoid foods that have been cooked.
The government-endorsed DASH Diet took the top spot as the best diet overall. Three diets tied at number two, excelling in all measures U.S News considered: the Mediterranean Diet, the TLC Diet, and Weight Watchers.
For a complete list of the new diet rankings, please visit:
A woman’s body shape – often described as pear, apple or hourglass – is usually determined by the amount of fat in various regions of the body including the bust, waist, arms and hips. New research from Emory University School of Medicine suggests that these patterns of fat distribution may help predict arterial stiffness – a precursor to cardiovascular disease.
Stiff arteries make the heart work harder to pump blood and are associated with atherosclerosis, or the buildup of plaques in vessels that can block blood flow and cause a heart attack.
Noting that fat distribution generally differs between black and white women’s bodies, researchers enlisted 68 black women and 125 white women, all middle-aged, to see whether these patterns could help assess cardiovascular risk.
Using skin calipers, the researchers measured subcutaneous fat in seven sites: the upper chest; midaxillary, or the side of the torso just under the armpit; triceps, or the back of the arm; subscapular, or on the back just below the shoulder blade; abdominal; suprailiac, or just above the front of the hip bone; and the thigh.
“Black women have higher rates of cardiovascular disease than white women and are more likely to die from it,” says Eapen. “Black and white women also have different patterns of fat distribution, so we were interested in measuring these pockets of fat at various regions of the body to evaluate whether it might be helpful in predicting cardiovascular risk between the two groups. Our hope was to evaluate whether a quick, easy-to-use clinical tool could aid in further risk stratifying our female patients.”
The study also assessed the arterial stiffness of the women, adjusting for heart rate.
As a group, the black women had greater arterial stiffness than the white women. They also had more subcutaneous fat in the armpit, triceps, shoulder blade and hip bone areas.
In addition, they also found specific race dependent pockets of fat that could be related to arterial stiffness – fat measurements in the triceps area could predict increased arterial stiffness in black women, while fat in the suprailiac areas was a predictor in white women.
Content contributed in part by Sarah Goodwin, Emory’s Center for Health Discovery and Well Being.
The report was published in the Oct. 22 issue of Population Health Metrics. Edward Gregg, Emory adjunct professor of global health, and David Williamson, Emory visiting professor of global health, were co-authors.
The CDC’s projections have been a work in progress. The last revision put the number at 39 million in 2050. The new estimate takes it to the range of 76 million to 100 million.
The growth in U.S. diabetes cases has been closely tied to escalating obesity rates. A corresponding rise in diabetes has even prompted researchers to coin a new hybrid term: diabesity.
“There is an epidemic going on that, if left unchecked, will have a huge effect on the U.S. population and on health care costs,” says K. M. Venkat Narayan, MD, MSc, MBA, professor of global health and epidemiology at the Rollins School of Public Health, who came to Emory from the CDC’s Division of Diabetes Translation. “The numbers are very worrying.”
K. M. Venkat Narayan, MD, MSc, MBA
Narayan also heads the Emory Global Diabetes Research Center, which aims to find solutions to the growing global diabetes epidemic. The Center serves as the research leader and hub for population-based research and large intervention trials throughout South Asia and globally.
“Whatever we do, the fruits of our research have to be available to people everywhere,” says Narayan.
Read more about Dr. Narayan’s global efforts and diabetes research underway at Emory.
Hear Dr. Narayan talk about the Global Diabetes Research Center.
Briefly, they found that increased appetite and insulin resistance can be transferred from one mouse to another via intestinal bacteria. The results were published online by Science magazine.
Previous research indicated intestinal bacteria could modify absorption of calories, but Gewirtz and his colleagues showed that they influence appetite and metabolism (in mice)
“It has been assumed that the obesity epidemic in the developed world is driven by an increasingly sedentary lifestyle and the abundance of low-cost high-calorie foods,” Gewirtz says. “However, our results suggest that excess caloric consumption is not only a result of undisciplined eating but that intestinal bacteria contribute to changes in appetite and metabolism.”
A related report in Nature illustrates how “next generation” gene sequencing is driving large advances in our understanding of all the things the bacteria in our intestines do to us.
Gewirtz’s laboratory’s discovery grew out of their study of mice with an altered immune system. The mice were engineered to lack a gene, Toll-like receptor 5 (TLR5), which helps cells sense the presence of bacteria.
Researchers at the Winship Cancer Institute of Emory University have found that the hormone adiponectin may reduce the ability of cancer cells to migrate from the breast and invade other tissues. Adiponectin appears to protect against the effects of obesity on metabolism, the heart and blood vessels, the researchers say.
Fat cells make up most of the breast tissue, and some of the hormones produced by fat cells can have tumor-stimulating effects. Previous studies have shown that women with high body mass index (highest fifth) have double the death rate from breast cancer compared to those in the lowest fifth.
Dipali Sharma, PhD
The key to translating this research for patient care lies in finding a way to increase a person’s adiponectin, says Dipali Sharma, PhD, assistant professor of hematology and medical oncology at Winship.
Currently, Winship scientists are testing a molecule found in certain foods that appears to mimic the effects of adiponectin. The molecule is found in grapes, cabbage and green tea.