Oct. 16, 2012

Europeans at Decreased Risk of Lupus Nephritis

European genetic ancestry is associated with a decreased risk of lupus nephritis
Richman IB, Taylor KE, Chung SA, Trupin L, Petri M, Yelin E, Graham RR, Lee A, Behrens TW, Gregersen PK, Seldin MF, and Criswell LA. (2012). Arthritis & Rheumatism 64: 3374-3382.

What is the topic?

African-Americans, Hispanics, and East Asians with lupus are at increased risk of developing kidney involvement as compared to individuals of European descent. This difference may be based in genetic ancestry, specific genes, and/or other factors.

What did the researchers hope to learn?

The researchers hoped to determine whether differences in genetic ancestry and/or specific genes contribute the decreased risk of developing lupus nephritis among individuals of European descent.

Who was studied?

Patients with lupus were recruited for participation in the study from the University of California at San Francisco (UCSF) Lupus Genetics Project and the Autoimmune Biomarkers Collaborative Network. A subset of the UCSF patients participated in the Lupus Outcomes Study. They were recruited from a variety of settings at UCSF and Johns Hopkins University, including academic medical centers, as well as community hospitals (San Francisco, California), and lupus support groups (nationwide).

How was the study conducted?

The primary outcome to be determined for each study participant was the presence of lupus nephritis, according to the American College of Rheumatology criteria. The following variables and their relationship to the presence of lupus nephritis were evaluated: lupus disease duration, sex, and socioeconomic status (as determined by self-reported education attainment and personal income, as well as U.S. census-determined neighborhood poverty).

Blood or saliva (if blood not available) were used to obtain DNA. DNA was then used to determine the genetic ancestry (where each person’s genes originated from) of each study participant (South Asia, East Asia, European, African, and Amerindian). In addition, a total of 14 known lupus susceptibility genes were examined for their possible role in lupus nephritis development.

What did the researchers find?

Most (92%) of the participants were female and they had lupus for about six years. About 62% of them were of European ancestry, while 16% were Africans, 11% were East Asians, 7% were Amerindians, and 4% were of South Asian descent. About 34% of the participants had a history of lupus-related kidney disease. East Asians had the highest prevalence (59%) of kidney disease, while those of European descent had the lowest (23%).

Among the individuals with lupus for whom socioeconomic status was available (n=1167), 23% had completed high school or less, 40% had some college education or a technical degree, and 37% had a college diploma or professional degree. Overall, 9% of participants lived in a neighborhood where > 30% of the residents earned below 125% of the income designated as the federal poverty level.

Additional analyses revealed similar (although less powerful) results when, instead of ancestry as defined by genetic markers, self-determined ethnicity was used, or when adjustment for other ancestries was performed. When measures of socioeconomic status or lupus susceptibility genes were also included in the analysis, the substantially decreased observation of lupus nephritis among Europeans persisted.

What were the limitations of the study?

First, the researchers examined only a relatively small number of genetic markers; other genes could still explain the ancestry-related susceptibility to lupus nephritis. Second, the candidate genetic data for lupus nephritis were not available for all participants. Third, environmental or social factors that were not measured could have influenced the results. Finally, there is such a degree of relationship between some ethnic groups and socioeconomic status, that socioeconomic factors could still be important in predisposing the development of lupus nephritis.

What do the results mean for you?

The results suggest that European ancestry may protect against the development of lupus nephritis, but how exactly this occurs is currently unknown. The results also suggest that socioeconomic status plays a smaller role in the development of lupus nephritis than does ancestry.


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