Gene variants found associated with human immune system, autoimmune disease

September 27, 2013

Numerous studies have reported that certain diseases are inherited. But genetics also plays a role in immune response, affecting our ability to stave off disease, according to a team of international researchers. The new findings, from the SardiNIA Study of Aging, supported in part by the National Institute on Aging (NIA) at the National Institutes of Health, are published in the Sept. 26, 2013 issue of Cell.

The SardiNIA researchers found 89 independent gene variants on the genome associated with regulating production of immune system cells. Five of these sites for the gene variants coincide with known genetic contributors to autoimmune diseases, and extend previous knowledge to identify the particular cell types that are affected by these genes.

"We know that certain diseases run in families. From this study, we wanted to know the extent to which relative or susceptibility to disease is inherited in families," said David Schlessinger, Ph.D., chief of NIA's Laboratory of Genetics. "If your mother is rarely sick, for example, does that mean you don't have to worry about the bug that's going around? Is immunity in the genes? According to our findings, the answer is yes, at least in part."

The study team, led by Francesco Cucca, M.D., director of the National Research Council's Institute of Genetic and Biomedical Research in Italy, discovered that variants in particular genes had very significant effects on the levels of one or more particular types of immune system cells. A number of these genes are also implicated in risk for various , including , multiple sclerosis, , and .

Understanding the genes affecting immune system cells and risk for autoimmune disease is the first step in developing therapies that are personalized according to an individual's needs, although more research is needed to further characterize the role genetics plays in the complex dynamics of the immune system, the researchers pointed out.

The human immune system is a complex network of cells, tissues, and organs working together to fight disease and keep us at optimal health and function. Our first line of defense, the innate immune system, includes barriers, like skin and mucus as well as specific cells and molecules providing a prompt but nonspecific response to harmful germs—pathogens—preventing them from entering the body or eliminating them rapidly after infection. The second line of defense, the adaptive immune system, engages the body to produce, store, and transport cells and molecules providing more specific responses to combat pathogens. The immune system has evolved to reject pathogens and even some cancers, but high levels of immune function can also make the body prone to autoimmune disease. Autoimmune diseases occur when the body uses the immune system against itself, attacking normal, healthy cells.

The number of adaptive available to attack a pathogen or, in the case of autoimmune disease, attack healthy cells, is what appears to be regulated by genetics. The SardiNIA research team tested the heritability of this using a -wide association study, looking at approximately 8.2 million variants in blood samples taken from 1,629 Sardinians.

Small, single-letter variations in genes naturally occur throughout the DNA code and are generally without effect on any specific trait. However, in some instances, scientists find that a particular variant is more common among people with a trait or disease.

In the analyses, researchers identified 89 independent variants and 53 sites associated with immune cell characteristics. Most of these associations were previously undiscovered. Some had been identified before in other studies, but without firm statistical significance. The researchers compared their findings with data in public repositories, and in some cases, found that these had already been associated with autoimmune disease.

This finding is the most recent of several discoveries made by the SardiNIA study itself and in conjunction with other groups in international consortia. Previous findings identified gene associations with height, fasting blood sugar, cholesterol and other fats in the blood, beta-thalassemia (a blood disorder), and uric acid levels, which can contribute to gout and risk of heart and kidney disease.

One of the unique features of the investigation is its study population—the Sardinians. "The lineage of most Sardinians goes back approximately 20,000 years, to the Mediterranean island's original settler population—and an ideal group for this type of research," said Cucca. "We have learned that in case after case, findings in Sardinia have been applicable world-wide."

Researchers note that understanding the genetics behind response and autoimmune disease may have future implications on therapeutic targets, especially in the treatment of autoimmune disease.

Explore further: Body's 'safety procedure' could explain autoimmune disease

Related Stories

Body's 'safety procedure' could explain autoimmune disease

September 5, 2013
Monash University researchers have found an important safety mechanism in the immune system that may malfunction in people with autoimmune diseases, such as Multiple Sclerosis, potentially paving the way for innovative treatments.

Scientists find link between allergic and autoimmune diseases in mouse study

June 4, 2013
(Medical Xpress)—Scientists at the National Institutes of Health, and their colleagues, have discovered that a gene called BACH2 may play a central role in the development of diverse allergic and autoimmune diseases, such ...

Scientists discover new mechanism regulating the immune response

June 28, 2013
Scientists at an Academy of Finland Centre of Excellence have discovered a new mechanism regulating the immune response that can leave a person susceptible to autoimmune diseases.

Researchers identify new functions for autoimmune disease 'risk' gene

July 19, 2013
Researchers at the University of Minnesota have identified infection-fighting and inflammation-suppressing functions for a gene associated with human autoimmune disease.

Autoimmune disease strategy emerges from immune cell discovery

September 9, 2013
Scientists from UC San Francisco have identified a new way to manipulate the immune system that may keep it from attacking the body's own molecules in autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and ...

Turning to parasites as potential disease fighters

September 9, 2013
(Medical Xpress)—There is a new weapon in the fight against autoimmune diseases such as Type 1 diabetes, rheumatoid arthritis, Crohn's disease and lupus, the common trait of which is an immune system that attacks its own ...

Recommended for you

A math concept from the engineering world points to a way of making massive transcriptome studies more efficient

November 17, 2017
To most people, data compression refers to shrinking existing data—say from a song or picture's raw digital recording—by removing some data, but not so much as to render it unrecognizable (think MP3 or JPEG files). Now, ...

Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)

November 15, 2017
The first genetic mutation that appears to protect against multiple aspects of biological aging in humans has been discovered in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, report Northwestern ...

Genetic variant prompts cells to store fat, fueling obesity

November 13, 2017
Obesity is often attributed to a simple equation: People are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. New research ...

Discovering a protein's role in gene expression

November 10, 2017
Northwestern Medicine scientists have discovered that a protein called BRWD2/PHIP binds to histone lysine 4 (H3K4) methylation—a key molecular event that influences gene expression—and demonstrated that it does so via ...

Twin study finds genetics affects where children look, shaping mental development

November 9, 2017
A new study co-led by Indiana University that tracked the eye movement of twins finds that genetics plays a strong role in how people attend to their environment.

Boy with rare disease gets brand new skin with gene therapy

November 8, 2017
Doctors treating a critically ill boy with a devastating skin disease used experimental gene therapy to create an entirely new skin for most of his body in a desperate attempt to save his life.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.