Racial disparities noted in immune system genes

University of Pittsburgh study focuses on genes regulating the inflammatory response

Specific variants in genes that encode proteins regulating inflammation may hold a key to explaining a host of disease processes known to cause increased risk of illness and death among African Americans, according to a study from the University of Pittsburgh’s Graduate School of Public Health (GSPH). The study, “Differential Distribution of Allelic Variants in Cytokine Genes Among African Americans and White Americans,” appears in the Dec. 1 issue of the American Journal of Epidemiology.

“We found that African Americans were significantly more likely to carry genetic variants known to stimulate the inflammatory response,” said Roberta B. Ness, M.D., M.P.H., professor and chair of the department of epidemiology at GSPH and the study’s primary author. “At the same time, genotypes known to dampen the release of anti-inflammatory proteins were more common among African Americans. This is kind of a double whammy.”

Researchers examined the race-specific distribution of allelic variants in cytokine genes known to promote inflammation. Chromosomes and genes occur in alternative forms, and these alternative genetic forms are called alleles. Cytokines are proteins that are secreted by immune system cells that regulate the body’s immune response to injury and illness.

Inflammation is believed to be a fundamental component of heart attack, stroke, diabetes and kidney disease, all of which strike African Americans in higher proportions than whites. Other disorders associated with the inflammatory response include premature labor, transplant rejection and autoimmune disorders such as multiple sclerosis and scleroderma – again, all more common among African Americans.

Specifically, scientists compared genetic data on 179 African-American and 396 white women who sought prenatal care and delivered uncomplicated, single, first births at Magee-Womens Hospital of the University of Pittsburgh Medical Center between 1997 and 2001. Blood samples were analyzed for a multitude of functionally relevant allelic variants in cytokine-regulating genes. Among these were several genes regulating the immune system proteins interleukin-1, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interleukin-10, interleukin-18 and tumor necrosis factor-alpha.

“In the past, people looked at one or two variants,” said Dr. Ness. “We looked at a whole host, and saw trends that perhaps point to some evolutionary-mediated change in the human genome that has had an impact on inflammation.”

Other factors also play an important role in the well-documented health disparities between African Americans and whites, stressed Dr. Ness. “Socioeconomic status, access to health care, racism, community-based issues and health behaviors are critical components of racial disparities in health,” she said. Among study participants, black women were younger, heavier, less likely to smoke and of lower socioeconomic status.