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Blacks share many genetic risks for IBD with whites, Asians
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Researchers have performed a comprehensive analysis of genetic risk factors for inflammatory bowel disease in blacks and found this population shares many genetic variants also associated with the disease in whites.
“This study is the culmination of over a decade of work,” Steven Brant, MD, director of the Johns Hopkins Meyerhoff IBD Center, said in a press release. “We hope it’s the first of many steps to better understand and treat these debilitating diseases.”
Because previous IBD genetics studies have focused on white and Asian populations, Brant and colleagues conducted a genetic mapping study using the Immunochip, a custom Illumina array of approximately 200,000 single nucleotide polymorphisms, to determine whether the 163 IBD susceptibility loci in whites are shared by blacks.
“We also studied whether there are regions of the genome that cause or protect IBD risk in African Americans that arise from either their West African or European genetic ancestries,” Brant said.
From 34 U.S. IBD centers, they enrolled 1,088 black patients with Crohn’s disease, 361 with ulcerative colitis, 62 with an unknown type of IBD and 1,797 non-IBD controls (some of whom also were enrolled from other Immunochip studies). A total of 130,241 autosomal SNPs from whole-blood samples were analyzed.
“Clearly, there are differences with disease presentations with IBD in African Americans,” Subra Kugathasan, MD, from Emory University School of Medicine, said in the press release. According to the study, IBD prevalence is lower in blacks compared with whites, and sibling risk is 2.5% vs. 4.6%, respectively. “We hope to have genetic explanations for this by expanding studies in African Americans,” Kugathasan said.
The investigators found risk factors for CD in blacks were associated with gene variants among NOD2, interleukin-23 receptor and a region on chromosome 5 called 5p15.1, which are “three of the most highly associated regions for [CD] in whites,” according to the press release. They also found that blacks share the same “dominant region for [UC] genetic risk … the human leukocyte antigen region,” with whites and Asians, but found no evidence that the major risk variant for UC in Europeans affects the black population.
Possible novel variations were identified at IL-12 cytokine subunit, a major IBD gene, and at chromosomes 2 and 3, which are previously unidentified regions, the release said. Regions on four autosomal chromosomes showed evidence of association with IBD risk, which “appears to come from the Caucasian ancestral genome that makes up 20% of the African American genome overall or, conversely, from unique African protective variants as demonstrated in the chromosomal 17 region within immune regulatory genes STAT3 and STAT5.”
Finally, analysis of cellular pathways linked to development of IBD showed blacks share major pathways — those related to cytokines, chemokines and JAK-STAT — with whites. “However, the top pathway for [UC] in African Americans and fourth of importance to both [CD] and IBD overall was related to measles infection, a pathway not previously found important to IBD in whites,” the release said. “Conversely, not found in IBD in African Americans was involvement of the Leishmania infection pathway, the second-strongest pathway for IBD in whites. Interestingly, African trypanosomiasis infection — the cause of African sleeping sickness — was also found to be a significant and unique pathway for [UC] in African Americans.”
“The hope for genetic advances is that we will be able to develop new therapies and more personalized approaches to managing these chronic and potentially debilitating diseases,” Dermot McGovern, MD, from Cedars-Sinai Medical Center, said in the press release. “These benefits should be available to all sections of society. This study is important, as it extends these possible advances to the African American population, who may be at risk of more severe IBD.” – by Adam Leitenberger
Disclosure: The researchers report no relevant financial disclosures.
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