Specific Changes in Genetic Sequence of Glucocorticoid Receptor Linked to Lupus in Chinese Study

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by Alice Melão |

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Immune system

Two specific variations in the genetic sequence of the glucocorticoid receptor — which determines how well glucocorticoid regulates metabolism and other key processes — were seen to markedly increase a person’s risk of systemic lupus erythematosus (SLE), a study conducted in China reports.

Published in the International Journal of Rheumatic Diseases, the study — “Association of glucocorticoid receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population” — suggests that glucocorticoids “may play a major role” in lupus development.

Glucocorticoids are hormones produced by the adrenal gland, which regulate processes like metabolism, cardiovascular function, and immune responses, among others.

These hormones have powerful anti-inflammatory and immunosuppressive activities, and are a first-line therapy for a wide range of autoimmune and inflammatory diseases, such as lupus, ulcerative colitis, and rheumatoid arthritis.

But how well glucocorticoid works depends greatly on the glucocorticoid receptor (GR). Changes, or variants, in the genetic sequence of this receptor may influence a person’s sensitivity to glucocorticoids.

Studies point to an association between the GR and the development of lupus. But data collected so far is incomplete, and studies have not addressed how single nucleotide variations (changes in the genetic sequence) in the GR gene might predispose people to this auto-immune disease.

Researchers at the Anhui Medical University, in China, investigated genetic alterations in the GR gene and how they influenced lupus development. The study included 400 Chinese lupus patients and 400 participants with no history of autoimmune diseases.

Variations of a single nucleotide (the basic structural unit and building block for DNA) in two different places on the GR gene, identified as rs6865292 and rs9324921, were associated with lupus development in this group.

Indeed, individuals who had a C instead of a T in the rs6865292 location, and those with an A instead of a C in rs9324921 were 32 percent more likely to have lupus. Two other genetic modifications, identified as rs7701443 and rs4607376, were found to be protect against lupus.

No association was found between these genetic variations in the glucocorticoid receptor and the development of lupus nephritis, or kidney inflammation caused by SLE.

“The study indicates that GR genetic polymorphisms may play a major role in the pathogenesis and development of SLE,” the researchers concluded. They also suggested lupus risk in a person could be identified early by looking for GR genetic variants.

Additional studies in larger groups of patients that address how GR gene modifications affect patients are warranted, they added.