Papers of the Month
Extramural
By Sara Amolegbe
Novel mechanism for manganese regulation in the brain
NIEHS grantees showed that brain manganese is regulated by activity of the gene SLC30A10 in the digestive system. This finding provides a novel mechanism for how manganese levels are normally regulated and suggests that changes to SLC30A10 activity in the digestive system may affect neurological outcomes from manganese exposure.
Previous studies have shown that loss of function of the gene SLC30A10 in the whole body can cause manganese neurotoxicity, but how manganese is regulated is unclear. The researchers compared brain manganese levels in mice lacking SLC30A10 in the whole body to mice lacking SLC30A10 in the liver, brain, and gastrointestinal tract.
The researchers observed the unexpected result that, under normal body conditions, activity of SLC30A10 in the gastrointestinal tract and liver, and not the brain or just the liver, regulated brain manganese. They also found that expression of SLC30A10 in the brain became important when tissue manganese levels increased. With increased manganese exposure, activity of SLC30A10 in the brain reduced manganese levels and protected against neurotoxicity.
The results described previously unknown complexities in the control of manganese in the brain under normal and elevated exposure conditions. According to the authors, this might have important implications for treatment of those exposed to toxic amounts of the metal, because the work raised the possibility that drugs that enhance levels or activity of SLC30A10 in the digestive system might increase manganese excretion before it reaches the brain.
Citation: Taylor CA, Hutchens S, Liu C, Jursa T, Shawlot W, Aschner M, Smith DR, Mukhopadhyay S. 2019. SLC30A10 transporter in the digestive system regulates brain manganese under basal conditions while brain SLC30A10 protects against neurotoxicity. J Biol Chem 294(6):1860–1876.
Teasing out genetic and environmental roles in diseases
Using a large health insurance database, NIEHS grantees identified genetic and environmental contributions to hundreds of disease-related conditions, ranging from cardiovascular illness and neuromuscular diseases to skeletal conditions. According to the authors, the study went beyond the traditional one-disease-at-a-time approach and analyzed genetic and environmental contributions to hundreds of the most common conditions.
Researchers estimated the genetic and environmental contributions of 560 disease-related conditions from health insurance data that included 56,393 twin pairs and 724,513 sibling pairs among more than 44 million individuals. They assessed environmental factors by linking individuals to location-specific data on air quality, temperature, and socio-economic status. Nearly 40 percent of the conditions in the study had a genetic component, whereas 25 percent were driven at least in part by factors found in a shared living environment.
Four of five cognitive disorders had a genetic component, which demonstrated the greatest degree of heritability. Connective tissue diseases had the lowest degree of genetic influence. Of all disease categories, eye disorders carried the highest degree of environmental influence, with 27 of 42 diseases showing such an effect. This was followed by respiratory diseases, with 34 of 48 conditions showing an effect caused by sharing the same environment.
In total, 145 of 560 diseases were modestly influenced by socio-economic status derived by zip code, with morbid obesity being the most significantly linked to socio-economic status. Of the full range of disease-related conditions, 36 diseases were influenced, at least in part, by air quality, and 117 were affected by changes in temperature.
Citation: Lakhani CM, Tierney BT, Manrai AK, Yang J, Visscher PM, Patel CJ. 2019. Repurposing large health insurance claims data to estimate genetic and environmental contributions in 560 phenotypes. Nat Genet 51(2):327–334.
Novel in-home air pollution sensor for community-based research
NIEHS grantees developed a low-cost, portable, in-home air sampling platform to characterize indoor pollutants. They highlighted the resources and maintenance considerations necessary to support community-based research goals.
Compared with previous indoor platforms, the Environment Multi-pollutant Monitoring Assembly (EMMA) tool developed by the grantees presented a relatively quiet, nonintrusive model for in-home sampling that did not distract participants from daily activities and was easily placed into main living spaces.
Although the sensors successfully collected real-time measurements for more than 18 months, the researchers experienced issues with maintenance of EMMA components. They found that costs of sensor maintenance were low upfront but increased with study duration. They also found that achieving quality low-cost sensor data required resources that were not available in communities without support from scientific groups.
According to the authors, development of high quality and affordable real-time sensors provides new opportunities to conduct research and inform individuals or communities on daily health risks. However, they emphasized that lower cost sensors should be placed with caution because of financial and resource costs that greatly exceed sensor costs. They also found that community-based participatory research strategies and collaboration between scientific and nonscientific groups could produce optimal data.
Citation: Gillooly SE, Zhou Y, Vallarino J, Chu MT, Michanowicz DR, Levy JI, Adamkiewicz G. 2019. Development of an in-home, real-time air pollutant sensor platform and implications for community use. Environ Pollut 244:440–450.
Heart disease hospitalizations spiked after Hurricane Katrina
A spike in cardiovascular disease (CVD) hospitalizations lasting more than a month was observed in Louisiana after Hurricane Katrina, according to an NIEHS-funded study. The increase in hospitalization rates was higher among older black adults compared with older white adults.
Using data from the Centers for Medicare and Medicaid Services, the team assembled a database with daily hospitalization rates for all CVD hospitalizations in three Louisiana parishes affected by Hurricane Katrina — Orleans, Jefferson, and East Baton Rouge. They compiled data over 710 days before, during, and after the hurricane and included demographic and population measures in their analysis using U.S. Census data and American Community Survey estimates.
The researchers found that CVD hospitalization rates were stable or declining in each parish, then rose immediately after Katrina made landfall in Orleans and Jefferson parishes. Both parishes were severely affected by the hurricane and subsequent floods. Hospitalization rates peaked in the Orleans parish on the sixth day after landfall, increasing from an average of 7.25 to 18.5 cases per day per 10,0000 adults aged 65 years or older. The rates increased to 26.3 cases per day per 10,000 people in older black adults compared with 16.6 cases in the older white adults. The rates returned to pre-landfall levels after about two months.
In the East Baton Rouge parish, which was not as hard hit but hosted many of the evacuees, CVD hospitalization rates were consistently higher on average for black adults than white adults, but no significant changes in CVD hospitalization rates were noted after landfall.
Citation: Becquart NA, Naumova EN, Singh G, Chui KKH. 2019. Cardiovascular disease hospitalizations in Louisiana parishes' elderly before, during and after Hurricane Katrina. Int J Environ Res Public Health 16(1).
(Sara Amolegbe is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)
