Immune-system Gene Variations May Increase Risk of Lupus in Caucasians, Study Reports

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Lupus and women

Certain variations in immune-system genes may be associated with an increased risk of Caucasians developing systemic lupus erythematosus (SLE), according to a study

The research, “Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune diseases: a meta-analysis,” was published in Scientific Reports.

The immune system is composed of complex networks that enhance its ability to ferret out and respond to threats. One network is known as the complement system. It works with antibodies to help the immune system defend against pathogens.

As the name implies, the complement system includes a number of players. One is the C4 protein, which plays “a pivotal role in the activation of immune defenses and the clearance of immune complexes,” researchers wrote.

Previous studies have shown that deleting a gene that’s involved in the complement C4 pathway can lead to autoimmune or inflammatory disorders. The C4A and C4B genes encode the C4 protein.

The human body can repeat, or copy, genes — a capability known as copy number variation, or CNV. The standard copy sequence is two genes, one from the father and one from the mother.

But sometimes there is only one copy of a gene, and at other times, three or more copies. This has led scientists to believe that CNV is related to several diseases — although gene-copy differences can also represent simple genetic variation, or what makes us different from others.

The combined impact that the C4A and C4B genes, the C4 protein, and CNVs have on people’s susceptibility to autoimmune diseases has remained far from clear, however.

Researchers performed a meta-analysis of 12 scientific-journal articles to seek insight into the roles that C4A and C4B, C4 and CNVs play in the development of autoimmune diseases among different ethnic groups. The research they analyzed, including 16 case studies with controls, covered Caucasians and Asians.

“In our meta-analysis of 8,663 cases and 11,099 controls in 16 studies from 12 articles, we drew a general conclusion that C4 and C4A CNVs are tightly associated with autoimmune diseases, especially with SLE,” the researchers wrote.

The team found that people with certain variations in their C4 and C4A genes were predisposed to autoimmune disorders. The association was strongest among Caucasians.

Overall, the results suggested that low C4 and C4A CNVs may cause susceptibility to autoimmune diseases, especially SLE, in Caucasians.