Elevated PRKCB Gene Levels May Play Protective Role in Lupus Patients, Chinese Study Shows

Jose Marques Lopes, PhD avatar

by Jose Marques Lopes, PhD |

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C1q role in lupus

The PRKCB gene is significantly more expressed in lupus patients than in healthy controls, a new Chinese study shows. But the gene appears to have a protective role, as patients with higher PRKCB expression have lower disease activity scores.

The research, “Increased expression of PRKCB mRNA in peripheral blood mononuclear cells from patients with systemic lupus erythematosus,” appeared in the journal Annals of Human Genetics.

The study’s senior authors were Sen Yang and Yujun Sheng, from the Institute of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, and Yong Cui, from the Department of Dermatology, China-Japan Friendship Hospital, Beijing, in China.

The exact mechanisms underlying lupus are still unclear. Systemic lupus erythematosus (SLE) is the most common of the four types of the disease, and is what most people mean when they refer to lupus. Genetic factors may play a key role, as more than 66 percent of cases are hereditary.

Recent work revealed a variety of genes involved in lupus. One of these genes is PRKCB, whose rs16972959 polymorphism (variant of the same gene leading to different manifestations) is strongly associated with lupus. Immune cell types, such as B-cells and mast cells, display high levels of PRKCB messenger RNA (mRNA, the intermediate product in the conversion of DNA into proteins).

The scientists compared levels of PRKCB mRNA in peripheral blood mononuclear cells (PBMCs — blood immune cells with a round nucleus, such as lymphocytes and monocytes) of lupus patients and healthy controls. The association between PRKCB mRNA, SLE Disease Activity Index (SLEDAI), and manifestations of the disease were also studied.

The study used molecular biology techniques to examine the expression (production) of PRKCB mRNA in PBMCs of 60 lupus patients and 62 controls. The research team also studied if patients with the rs16972959 variant had more mRNA production, and whether they had increased disease activity.

The results showed that PRKCB mRNA levels were increased in lupus patients compared to healthy controls. But those with higher mRNA levels had significantly lower disease activity. Also, lower mRNA levels in lupus patients were observed in cases of a new rash and proteinuria (excessive levels of proteins in the urine).

Taken together, “the increased PRKCB mRNA level in SLE and negative linear correlation between PRKCB mRNA expression levels and [disease activity] indicated that PRKCB might act as a “protective” factor in this disease,” the team wrote.

The investigators did not find an association between the variant rs16972959 and PRKCB mRNA levels, “indicating that rs16972959 may not directly relate to mRNA expression levels of PRKCB in healthy controls and SLE cases, probably because of small sample sizes,” they wrote.

However, the results demonstrated that rs16972959 correlated with increased PRKCB expression in naïve (resting) and activated monocytes in Europeans.

In addition, the data suggested significant associations of rs16972959 with vasculitis (inflammation of the blood vessels) in lupus patients.

“These findings indicated that PRKCB might play important roles not only in the disease development, but also in the complex phenotypes of SLE,” the researchers concluded.