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Evidence Of A Common Genetic Component For IBD And ankylosing spondylitis
02 Aug 2007
As edited by Joint-Pain-Forum.com
Researchers and clinicians have widely noted an intriguing link
between some intestinal diseases and some forms of arthritis. In
particular, chronic inflammatory bowel disease (IBD) frequently
afflicts patients with ankylosing spondylitis (AS), marked by chronic
inflammation of the spine and the sacroiliac joints. Separately, both
IBD and AS have been shown to run in families. Yet, the specific
genetic susceptibility, and whether it is the same for both diseases,
remains a mystery.
For studying the genetic links between IBD and AS, the
citizens of Iceland are an ideal population. In contrast to not just
Americans but most other Europeans, Icelanders are strikingly
homogeneous with respect to environmental, cultural, and genetic
factors. What's more, Iceland boasts an extensive genealogic database,
collected by deCODE Genetics, containing records on every family in the
country, plus registries of all patients diagnosed with IBD and AS
spanning 50-year periods, along with a highly accessible health care
system. Leveraging these resources, researchers at Landspitali
University Hospital, Reykjavik, assessed the occurrence of IBD and AS
among relatives and the risk of inheriting either and both disorders.
Their results, featured in the August 2007 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), provide compelling evidence of a common genetic component for IBD and AS.
Comparing the data on all living Icelanders diagnosed with AS, 205
individuals, and all diagnosed with IBD, 1,352 individuals, with the
body of genealogic data on over 790,000 Icelanders, the researchers
found significant clustering of each condition within families,
extending over 6 generations. To strengthen these findings, they
calculated the risk ratio of each disorder for a relative of an
affected person, including spouses, as compared with the risk in the
population as a whole, for 10,000 sets of matched control subjects.
They also performed cross-risk ratios of AS for relatives of patients
with IBD and of IBD for relatives of patients with AS. Finally, they
calculated the kinship coefficient (KC) -- the probability that any 2
alleles, genes with specific positions on specific chromosomes, are
inherited from one common ancestor -- for all the patients with IBD and
all the patients with AS, and compared the KC values with 100,000 sets
of matched control subjects.
First-, second-, and third-degree
relatives of patients with AS had risk ratios of 94, 25, and 3.5,
respectively, indicating an increased risk of developing AS, while
first-, second-, and third-degree relatives of patients with IBD had
risk ratios for IBD of 4.4, 2.2, and 1.4, respectively. In addition to
confirming the genetic risk for AS and IBD independently, the study
found elevated cross-risk ratios between IBD and AS in both first- and
second-degree relatives. The cross-risk ratios for IBD in first- and
second-degree relatives of patients with AS were 3.0 and 2.1,
respectively, and, notably, were the very same for AS in first- and
second-degree relatives of patients with IBD. Overwhelmingly, findings
applied to blood relatives. Risk ratios for spouses were zero to
insignificant. The one exception was an increased risk of having
Crohn's disease in spouses of patients with Crohn's disease, suggesting
the possible role of an environmental factor.
Based on KC values, patients with IBD were more likely to be
related to each other than to population controls. The KC was
significant in relatives up to the fourth generation. Similar to the
findings from the risk analyses, even stronger relationships among AS
patients were evident throughout the first three generations.
Furthermore, patients with IBD and patients with AS were more closely
related to each other, even after exclusion of second-degree relatives
-- grandparents, grandchildren, and first cousins -- than were
population controls.
While this study indicates an inherited bond between the risk
of AS and IBD, the nature of this genetic abnormality is speculative.
"Our results provide strong evidence that a molecular-genetic approach
should be utilized in patients with these diseases," observes the
study's lead author, Dr. Bjarni Thjodleifsson. "If this approach proves
successful, this will open the possibility of identifying a common
early pathophysiologic event in both AS and IBD that may be amenable to
new and selective treatments."
----------------------------
Article adapted by www.Joint-Pain-Forum.com from original press release.
----------------------------
Article: "A Common Genetic Background for Inflammatory Bowel Disease
and Ankylosing Spondylitis: A Genealogic Study in Iceland," Bjarni
Thjodleifsson, Árni J. Geirsson, Sigurdur Björnsson, and Ingvar
Bjarnason, Arthritis & Rheumatism, August 2007; (DOI:10.1002/art.22812).
Source: Amy Molnar
John Wiley & Sons, Inc.
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