Genetic Risk Factors for IBD Identified in African-American Population

Genetic Risk Factors for IBD Identified in African-American Population

In a new study entitled “Characterization of Genetic Loci That Affect Susceptibility to Inflammatory Bowel Diseases in African Americans,” researchers investigated the genetic causes for inflammatory bowel disease (IBD) in African-Americans in a comprehensive study. The study was published in the journal Gastroenterology.

Inflammatory bowel disease (IBD) is particularly prevalent among the African American population, a condition referred to as familial aggregation (the occurrence of more cases of a given disorder in close relatives of a person with the disorder, when compared to control families). However, the genetic causes underlying the predisposition are poorly defined.

In this new research, researchers at the Johns Hopkins University School of Medicine with colleagues at Emory University and Cedars-Sinai investigated the genetic risk factors for IBD in African Americans by performing the first in-depth analysis of this population’s genetic map. To this end, they recruited African American subjects with and without IBD from a wide network of IBD centers throughout the United States (specifically, 34 centers). The number of subjects evaluated in the study was above 1,500 African-American patients with IBD (1,088 with Crohn’s disease and 361 with ulcerative colitis) and included 1,797 African-Americans without IBD, as controls.

The study investigated first whether the 163 separate genetic variations determined as IBD risk factors in white Americans were also present in African Americans. Additionally, the team aimed at identifying new loci (regions within the genome) as IBD risk factors, specifically in the African American population, as Steven Brant, M.D., director of the Johns Hopkins Meyerhoff Inflammatory Bowel Disease Center and corresponding author of the study noted, “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.”

The team of scientists discovered that both white and African Americans share genomic loci highly associated with Crohn’s disease, specifically NOD2, interleukin 23 receptor (IL23R) and a region on chromosome 5 known as 5p15.1.

African Americans, just as caucasians and Asians, exhibit the same dominant region for ulcerative colitis genetic risk – the human leukocyte antigen (HLA) region. Notably, however, while the variations within the HLA region is the same between African Americans and Asians (specifically, Japanese and Korean ulcerative colitis), the same does not occur when compared to ulcerative colitis in Europeans. Accordingly, the study found no evidence for this region in Europeans to affect the African-American population. The team discovered novel variations at a major IBD gene – the interleukin (IL) 12 cytokine subunit, IL12B – and new regions (on chromosomes 2 and 3) associated with IBD and ulcerative colitis, respectively.

Dermot McGovern, M.D., of Cedars-Sinai Medical Center and co-senior author added, “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. 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.”

Authors identified cellular pathways that lead to IBD development, particularly the JAK–STAT, cytokine, and chemokine signaling pathways, as well as measles infection (newly identified in white population). In African-Americans, authors identified Leishmania infection pathway as an IBD risk factor (previously identified as the second-strongest pathway for IBD in whites). Additionally, a unique pathway in ulcerative colitis in African-Americans was African trypanosomiasis infection (responsible for African sleeping sickness).

The intricate genetic factors identified, either contributing as risk or protection factors from IBD in different populations, require further studies.