Genetic profiling can predict some lupus manifestations

Lupus Foundation of America

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What is the topic?

Numerous studies have established that genetics influences the development of lupus. Most existing studies have reported on genes that may increase an individual’s susceptibility to developing lupus. However, only few studies have examined the relationship between these “lupus susceptibility genes” and specific disease manifestations or disease severity. Examination of such relationships may help to define disease mechanisms and perhaps predict disease manifestations.

What did the researchers hope to learn?

The researchers hoped to learn about the relationship between the presence of specific lupus susceptibility genes and the development of specific disease manifestations. 

Who was studied?

Genetic samples were taken from a large number of people with lupus from different ethnic backgrounds.

How was the study conducted?

Genetic material was taken from 3675 European-derived lupus patients, as well as from 1566 African Americans, 1139 Asians, and 1426 Hispanic people with lupus from around the globe. Sixteen lupus susceptibility genes and 161 ethnic-specific genes from these samples were studied at the Oklahoma Medical Research Foundation (Oklahoma City, Oklahoma). Clinical data, such as information about arthritis, tissue inflammation (specifically, inflammation of the layer surrounding heart, lungs and abdomen), as well as kidney and blood disorders, were obtained from patients’ medical records. The researchers used advanced statistics to determine which clinical manifestations were most associated with specific lupus susceptibility genes. 

What did the researchers find?

The genetic samples were taken from European, African-American, Asian, and Hispanic lupus patients. Most of them were women with an average age of 26-34 at the time of lupus diagnosis. These patients experienced a wide variety of clinical manifestations of lupus, including arthritis, kidney disorder, blood disorder, skin rash, oral ulcers, and photosensitivity (sensitivity to ultraviolet light). 

Of the 16 lupus susceptibility genes studied, 5 were significantly associated with specific clinical manifestations of lupus. The most significant of these was the association between kidney disorder and the lupus susceptibility gene ITGAM or TNFSF4. ITGAM was also associated with discoid rash (a type of chronic rash seen in systemic lupus patients that usually leads to scarring). Additional significant associations were found between the following lupus susceptibility genes and clinical disease manifestations: FCGR2A and malar rash (a butterfly-shaped rash of the face), STAT4 and mouth ulcers, as well as IL21 and blood disorder (specifically, reduced number of white blood cells). 

Some associations were more pronounced within specific sets of ethnic patients. For example, the association between kidney disorder and ITGAM or TNFSF4 was mostly due to that occurring in the European-derived patients. An additional association was ethnic-specific – that between KIAA1542 and tissue inflammation in Hispanic patients. 

What were the limitations of the study?

The genetic markers used to identify lupus susceptibility genes in this study primarily identify genes in European-derived lupus patients. Therefore, the majority of associations (between lupus susceptibility genes and clinical disease manifestations) reported here are due to those found in European-derived lupus patients. This suggests that further studies are needed in order to identify useful genetic markers of lupus susceptibility genes in other ethnic groups. 

What do the results means for you?

As lupus nephritis is known to be a cause of significant morbidity, its association with a specific lupus susceptibility gene may pave the way for better prediction of nephritis in the future. Importantly, this study lends support to the feasibility of using genetic analysis to identify people with lupus at increased risk for developing specific clinical features of the disease. This study helps to pave the way towards strategies that may facilitate the development of effective personalized medicine in clinical rheumatology.

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus
Sanchez E, Nadig A, Richardson BC, Freedman BI, Kaufman KM, Kelly JA, Niewold TB, Kamen DL, Gilkeson GS, Ziegler JT, Langefeld CD, Alarcón GS, Edberg JC, Ramsey-Goldman R, Petri M, Brown EE, Kimberly RP, Reveille JD, Vilá LM, Merrill JT, Anaya JM, James JA, Pons-Estel BA, Martin J, Park SY, Bang SY, Bae SC, Moser KL, Vyse TJ, Criswell LA, Gaffney PM, Tsao BP, Jacob CO, Harley JB, Alarcón-Riquelme ME, and Sawalha AH. (2011). 
Annals of the Rheumatic Diseases 70: 1752-1757.