Gene difference affects inflammation response in people

Where your ancestors came from and the diseases they encountered over many years is likely to influence your immune system, a new study suggests.

Researchers have long known that people of European and African ancestry differ in their susceptibility to infections and diseases. But little is known about how much genetics and different lifestyle factors, such as alcohol intake and obesity, contribute to this.

Now a team of scientists from Roswell Park Comprehensive Cancer Centre in New York,US, reports the discovery of a genetic difference between people with African and European ancestry that affects how the immune system triggers inflammation.

They suspect the difference was driven by how the immune system evolved and, in particular, evolutionary pressure exerted by malaria on people who lived in Africa over thousands of years.

The finding could have implications for the health of people with African heritage, including the prevention and treatment of cancer and other chronic diseases.

To study how people’s immune systems respond to genetics and lifestyle, the researchers combined genetic, molecular and epidemiological data from 914 people with African ancestry, and 855 people with European ancestry. The participants came from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.

Their blood was analysed to detect 14 different chemical messengers called cytokines, which are involved in inflammation. There were significant differences in seven of those 14 chemical messengers between the two groups.

Lifestyle factors including age, education, obesity, smoking, alcohol use and even reproductive history could account for many of the differences, but the study also found a genetic variant that occurred mainly in the African group.

The variant controlled the levels of two key pro-inflammatory chemical messengers involved in recruiting white blood cells to sites of inflammation. Previous research suggests this variant evolved to protect African people from malaria.

The researchers say ‘ancestral footprints’ in the genome such as this one could be contributing to health problems for people with African ancestry. They add that inflammation has evolved as a response to injury and infection but is also implicated in several types of cancer and chronic disease.

One of the researchers, Christine Ambrosone, says the study was prompted by a suspicion that adaptation over millennia to protect African people from infectious diseases had resulted in a more robust immune response that might be linked to more aggressive breast cancer in the twenty-first century.

Her colleague Song Yao suggests the next step is to investigate the implications for cancer treatment outcomes.

“These findings indicate that evolutionary adaptation many thousands of years ago shaped our immune systems and may still have considerable influences on immune function today,” he says.

“The next research question we are pursuing is whether those evolutionary marks play any significant role in affecting breast cancer health disparities.”

The research was published in PLOS Genetics.