Genetics Linked to Lupus Complications
Genetics Linked to
Large multi-ethnic, multi-regional
study finds Hispanics at greater risk
of having serious kidney damage
Texas Hispanics with Systemic Lupus Erythematosus SLE) are
more likely to develop serious complications of kidney-damage
than other groups, researchers at The University of Texas
Medical School at Houston and four other universities have found.
Studies looked at the relative effects of genetic and socioeconomic
factors on the course and outcome of lupus in Hispanics,
African-Americans and Caucasians in Texas and Alabama.
Lupus is ... an inflammatory disease in which the immune
system fails to distinguish between its own cells and
those it considers to be enemies or foreign invaders.
The body turns on itself, strategically
attacking the skin, blood, joints and kidneys.
In more severe forms of Lupus, like SLE, other
organs and tissues also may be affected.
John Reveille, M.D., leads
research on effects of genetic
and socioeconomic factors on
the course and outcome of Lupus.
Photo by Ester Fant
The project is the largest multi-ethnic,
multi-regional and multi-institutional study of
Lupus to include a sizeable Hispanic component.
This is crucial to identifying distinct SLE
characteristics that could then be related
to a person's genetic make-up, believes
project co-investigator John Reveille,
M.D., professor and director of the Division
of Rheumatology and Clinical Immunogenetics
at the UT Medical School at Houston.
"We wanted to do these prospective studies
to look at women with lupus diagnosed
within the last five years," Reveille said.
Following patients over a nine-year period,
researchers tracked death, damage, disability and
disease activity, or the 4 D's, as Reveille calls them.
Reveille was surprised by findings from the LUMINA
(LUpus in MInority populations: NAture vs.
nurture) Project, which showed that Hispanic women:
- had a poorer prognosis overall,
- were more likely to have kidney
involvement and damage, and
- showed a more rapid rate of kidney failure.
"This bothered Dr. Alarcón and me a great deal," he said.
Together, Reveille and co-investigator Graciela Alarcón, M.D.,
professor of medicine at the University of Alabama at Birmingham
(UAB) Schools of Medicine and Public Health, have studied Lupus
for 15 years, trying to determine which is more important
in diagnosis, nature (genetics) or nurture (lifestyle).
"In the LUMINA study, we have recently included
the University of Puerto Rico, where we enrolled
71 Lupus patients, and launched a larger study,
PROFILE, with UT-Houston, UAB, Johns Hopkins
in Baltimore and Northwestern University in Chicago."
When the PROFILE study began looking at larger numbers
of Lupus patients over 900 total one issue still stood out.
Hispanics, specifically Texas Hispanics, tended to
develop renal-damage much faster than other groups.
Even when correcting for socio-demographic factors like income,
education and housing, and the known psychological factors
associated with lupus, the numbers told the same story
suggesting that it might still be more nature than nurture.
"We think that the AmerIndian genetic background of
Texas Hispanics is contributing to the higher incidence
of renal involvement and damage in this group," Reveille said.
It's not necessarily being Hispanic that's the issue, he said.
In fact, the majority of Lupus patients from Puerto Rico
had very mild Lupus and little renal involvement.
He believes the disparity between the two
groups is due to their genetic ancestry.
"Puerto Ricans are evenly made up of Spanish,
African and a lesser amount of AmerIndian genes,"
he said, "while Texas Hispanics in Houston have [a]
largely [amount of] AmerIndian and Caucasian genes."
Does this mean having AmerIndian
ancestry makes the Lupus prognosis worse?
"We're currently looking at this," Reveille said.
"We already know certain genetic markers are
tightly associated with lupus in different groups, but
they don't tell us why Texas Hispanics with Lupus
have a higher rate of kidney damage and failure."
African-American women, who, previous studies have shown,
have a higher rate of lupus overall, have been shown also
in the LUMINA project to fare worse than Caucasians.
Lupus is more frequent in non-Caucasians,
is a major disease that affects primarily young women
in their most productive years, and is potentially deadly.
"We know this much about lupus, but its general
impact in Hispanics isn't well understood because
there's been virtually no data," Reveille said.
Results of the studies were published in the December
issue of Lupus, and in February, Reveille was invited
to speak at the Hispanic National Caucus in Washington,
D.C., where he presented findings based on both
the PROFILE and LUMINA studies.
"This is becoming an issue that affects us all when we look
at the population trends in the United States and realize
Hispanics will be the majority group in 20 years," he said.
Both PROFILE and LUMINA are funded by
grants totaling more than $3 million from
the National Institute of Arthritis and
Musculoskeletal and Skin Disorders.
Caucasians, Hispanics and African-Americans
with SLE for less than five years may contact
Robert Sandoval, (713) 500-6870,
for information about participation in the studies.
The studies monitor the patients'
Lupus but do not offer free treatment.
By Kimberly Malone, Ph.D., Public Affairs